JP2014003919A - Transcobalamin ii gene product amount regulator - Google Patents
Transcobalamin ii gene product amount regulator Download PDFInfo
- Publication number
- JP2014003919A JP2014003919A JP2012140308A JP2012140308A JP2014003919A JP 2014003919 A JP2014003919 A JP 2014003919A JP 2012140308 A JP2012140308 A JP 2012140308A JP 2012140308 A JP2012140308 A JP 2012140308A JP 2014003919 A JP2014003919 A JP 2014003919A
- Authority
- JP
- Japan
- Prior art keywords
- transcobalamin
- gene product
- gene
- amount
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108010023603 Transcobalamins Proteins 0.000 title claims abstract description 64
- 102000011409 Transcobalamins Human genes 0.000 claims abstract description 41
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 38
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229960003080 taurine Drugs 0.000 claims abstract description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 208000024891 symptom Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 42
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 23
- 229930003779 Vitamin B12 Natural products 0.000 description 21
- 239000011715 vitamin B12 Substances 0.000 description 21
- 235000019163 vitamin B12 Nutrition 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 101150089431 TCN2 gene Proteins 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 210000000601 blood cell Anatomy 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 238000013519 translation Methods 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108091060211 Expressed sequence tag Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 201000003908 endometrial adenocarcinoma Diseases 0.000 description 2
- 208000029382 endometrium adenocarcinoma Diseases 0.000 description 2
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 102000018146 globin Human genes 0.000 description 2
- 108060003196 globin Proteins 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- YOZNUFWCRFCGIH-BYFNXCQMSA-L hydroxocobalamin Chemical compound O[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O YOZNUFWCRFCGIH-BYFNXCQMSA-L 0.000 description 2
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- 235000007672 methylcobalamin Nutrition 0.000 description 2
- 239000011585 methylcobalamin Substances 0.000 description 2
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 235000014102 seafood Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 125000002124 5'-adenosyl group Chemical group N1=CN=C2N(C=NC2=C1N)[C@H]1[C@H](O)[C@H](O)[C@H](O1)C* 0.000 description 1
- 102000011848 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Human genes 0.000 description 1
- 108010075604 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Proteins 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 description 1
- 208000009888 Adrenocortical Adenoma Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 1
- 241000473391 Archosargus rhomboidalis Species 0.000 description 1
- 241000796533 Arna Species 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 241000711404 Avian avulavirus 1 Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 201000010717 Bruton-type agammaglobulinemia Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100025240 CD320 antigen Human genes 0.000 description 1
- 102000046744 Calpain-3 Human genes 0.000 description 1
- 108030001375 Calpain-3 Proteins 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000238366 Cephalopoda Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010014568 Empyema Diseases 0.000 description 1
- 208000005431 Endometrioid Carcinoma Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 206010016935 Follicular thyroid cancer Diseases 0.000 description 1
- 208000021309 Germ cell tumor Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000572820 Homo sapiens MICOS complex subunit MIC60 Proteins 0.000 description 1
- 101001126977 Homo sapiens Methylmalonyl-CoA mutase, mitochondrial Proteins 0.000 description 1
- 101000891321 Homo sapiens Transcobalamin-2 Proteins 0.000 description 1
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000012528 Juvenile dermatomyositis Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 206010024305 Leukaemia monocytic Diseases 0.000 description 1
- 206010024612 Lipoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 102100030979 Methylmalonyl-CoA mutase, mitochondrial Human genes 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000238413 Octopus Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033892 Paraplegia Diseases 0.000 description 1
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000032930 Spastic paraplegia Diseases 0.000 description 1
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 206010050208 Teratospermia Diseases 0.000 description 1
- 208000002312 Teratozoospermia Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000021914 Transcobalamin deficiency Diseases 0.000 description 1
- 102100040423 Transcobalamin-2 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000016349 X-linked agammaglobulinemia Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000015234 adrenal cortex adenoma Diseases 0.000 description 1
- 201000003354 adrenal cortical adenoma Diseases 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 201000010415 childhood type dermatomyositis Diseases 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 235000006279 cobamamide Nutrition 0.000 description 1
- 239000011789 cobamamide Substances 0.000 description 1
- ZIHHMGTYZOSFRC-UWWAPWIJSA-M cobamamide Chemical compound C1(/[C@](C)(CCC(=O)NC[C@H](C)OP(O)(=O)OC2[C@H]([C@H](O[C@@H]2CO)N2C3=CC(C)=C(C)C=C3N=C2)O)[C@@H](CC(N)=O)[C@]2(N1[Co+]C[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C3=NC=NC(N)=C3N=C1)O)[H])=C(C)\C([C@H](C/1(C)C)CCC(N)=O)=N\C\1=C/C([C@H]([C@@]\1(CC(N)=O)C)CCC(N)=O)=N/C/1=C(C)\C1=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]1CCC(N)=O ZIHHMGTYZOSFRC-UWWAPWIJSA-M 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 208000028730 endometrioid adenocarcinoma Diseases 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 201000006608 esophagus squamous cell carcinoma Diseases 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 102000046079 human IMMT Human genes 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 235000004867 hydroxocobalamin Nutrition 0.000 description 1
- 239000011704 hydroxocobalamin Substances 0.000 description 1
- 229960001103 hydroxocobalamin Drugs 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 201000005282 malignant pleural mesothelioma Diseases 0.000 description 1
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 201000006894 monocytic leukemia Diseases 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000008518 non respiratory effect Effects 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000000064 prostate epithelial cell Anatomy 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 208000000943 scapulohumeral muscular dystrophy Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000003728 serous cell Anatomy 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 206010043688 thyroid adenoma Diseases 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 201000002956 transcobalamin II deficiency Diseases 0.000 description 1
- 108010083125 transcobalamin receptor Proteins 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、2−アミノエタンスルホン酸を含有することを特徴とする、トランスコバラミンIIの遺伝子産物量の調整剤に関する。 The present invention relates to a regulator for the gene product amount of transcobalamin II, which contains 2-aminoethanesulfonic acid.
ビタミンB12は、食事やサプリメント、医薬品から摂取され、体内に吸収された後、血中で直ちにキャリアタンパクであるトランスコバラミンと結合する。トランスコバラミンとしては、トランスコバラミンI、トランスコバラミンII及びトランスコバラミンIIIの三種類が知られており(非特許文献1)、血中ビタミンB12の約20%はトランスコバラミンIIと結合し、残りの大部分はトランスコバラミンIおよびトランスコバラミンIIIと結合している(非特許文献2)。 Vitamin B12 is taken from meals, supplements, and medicines, absorbed into the body, and then immediately combined with transcobalamin, which is a carrier protein, in the blood. As transcobalamin, three types of transcobalamin I, transcobalamin II and transcobalamin III are known (Non-patent Document 1), and about 20% of blood vitamin B12 binds to transcobalamin II and the remaining large amount. The part is couple | bonded with transcobalamin I and transcobalamin III (nonpatent literature 2).
トランスコバラミンIIは組織細胞へのビタミンB12供給に関与しており、ビタミンB12と結合したトランスコバラミンIIはトランスコバラミンレセプターを介して速やかに細胞内に取り込まれ、細胞内にてビタミンB12と分離する。一方、トランスコバラミンIは血中における貯蔵機能を有しており、通常の血中ビタミンB12濃度と相関する(非特許文献2)。ビタミンB12と結合したトランスコバラミンIIは、ホロ−トランスコバラミンIIと呼ばれ、血中ホロ−トランスコバラミンII量は食事による血中ビタミンB12摂取量に影響されることなく、一日中安定している(非特許文献3)。 Transcobalamin II is involved in the supply of vitamin B12 to tissue cells, and transcobalamin II bound to vitamin B12 is rapidly taken into the cell via the transcobalamin receptor and separated from vitamin B12 in the cell. On the other hand, transcobalamin I has a blood storage function and correlates with a normal blood vitamin B12 concentration (Non-patent Document 2). Transcobalamin II bound to vitamin B12 is called holo-transcobalamin II, and the amount of blood holo-transcobalamin II is stable throughout the day without being influenced by blood vitamin B12 intake from the diet (non- Patent Document 3).
トランスコバラミンIIが増加又は減少した場合、細胞内ビタミンB12濃度に影響を及ぼし、ビタミンB12依存補酵素であるメチルマロニルコエンザイムAムターゼ及びメチオニンシンターゼの代謝異常が引き起こされる恐れがある(非特許文献4)。さらに、トランスコバラミンII欠乏は、下痢、嘔吐等の消火器症状、巨赤芽性貧血、血小板減少などを引き起こすなど(非特許文献5)、トランスコバラミンIIの遺伝子産物量の変動(増加又は減少)や細胞内ビタミンB12濃度の異常は、様々な症状や疾病を伴っていることが報告されている(非特許文献6)。 When transcobalamin II is increased or decreased, the intracellular vitamin B12 concentration is affected, and there is a possibility that abnormal metabolism of methylmalonylcoenzyme A mutase and methionine synthase, which are vitamin B12-dependent coenzymes, is caused (Non-patent Document 4). . Furthermore, transcobalamin II deficiency causes fire extinguisher symptoms such as diarrhea and vomiting, giant erythroblastic anemia, thrombocytopenia, etc. (Non-patent Document 5). It has been reported that abnormalities in intracellular vitamin B12 concentration are accompanied by various symptoms and diseases (Non-patent Document 6).
細胞内ビタミンB12濃度を正常域に保つことは、ヒトの生体機能を維持し、健康維持・増進にとって必要であり、これには血中ビタミンB12濃度を正常域に保つのみでなく、トランスコバラミンIIの遺伝子産物量を安定させることが極めて重要である。しかしながら、これまでの多くの研究によっても、トランスコバラミンIIの遺伝子産物量を調整する医学的な治療方法は提供されていないし、その研究に供される試薬なども開発されていない。 Maintaining the intracellular vitamin B12 concentration in the normal range is necessary for maintaining the human biological function and maintaining and promoting health. This includes not only maintaining the blood vitamin B12 concentration in the normal range but also transcobalamin II. It is extremely important to stabilize the amount of gene product. However, many studies so far have not provided a medical treatment method for adjusting the amount of the gene product of transcobalamin II, and a reagent used for the study has not been developed.
これまでに、細胞内ビタミンB12濃度を安定させる方法として、血中ホロ−トランスコバラミンII量が低下している状態におけるチオラコバラミンの提供が知られている。また、ビタミンB12とグルタチオン前駆体とを同時に投与することにより、神経組織や血管内皮におけるコバラミンの細胞内プロセッシングを容易にする薬剤の提供が提案されている(特許文献1)。しかし、これらは、トランスコバラミンIIの遺伝子産物量を調整していないし、トランスコバラミンIIの遺伝子産物量の変動を伴う症状や疾病には対応できていない。 So far, as a method for stabilizing intracellular vitamin B12 concentration, provision of thiolacobalamin in a state where the amount of blood holo-transcobalamin II is reduced is known. In addition, it has been proposed to provide a drug that facilitates intracellular processing of cobalamin in nerve tissue and vascular endothelium by simultaneously administering vitamin B12 and glutathione precursor (Patent Document 1). However, they do not adjust the amount of transcobalamin II gene product and cannot cope with symptoms and diseases accompanied by fluctuations in the amount of transcobalamin II gene product.
ここで、2−アミノエタンスルホン酸は、魚介類に多く含まれる含硫アミノ酸で、ヒトでは心筋、筋肉、脾臓、脳、肺、骨髄などに存在しており、医療用医薬品、OTC医薬品、特別用途食品、その他の食品に広く使用されている。しかし、トランスコバラミンIIの遺伝子産物量を調整することは知られていない。 Here, 2-aminoethanesulfonic acid is a sulfur-containing amino acid that is abundant in seafood, and is present in human heart muscle, muscle, spleen, brain, lung, bone marrow, and the like. Used widely for food and other foods. However, it is not known to adjust the gene product amount of transcobalamin II.
本発明の目的は、トランスコバラミンIIの遺伝子産物量を調整するために用いる試薬、医薬品及び食品を提供することである。 An object of the present invention is to provide a reagent, a pharmaceutical and a food used for adjusting the amount of gene product of transcobalamin II.
本発明者らは、前記課題を解決すべく鋭意検討した結果、2−アミノエタンスルホン酸が、トランスコバラミンIIの遺伝子産物量を調整することを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that 2-aminoethanesulfonic acid adjusts the gene product amount of transcobalamin II, and completed the present invention.
即ち、本発明によれば、以下の発明が提供される。 That is, according to the present invention, the following inventions are provided.
(1)2−アミノエタンスルホン酸を含有することを特徴とする、トランスコバラミンII遺伝子産物量の調整剤。
(2)トランスコバラミンIIの遺伝子産物量の変動を伴う症状及び/又は疾病に対する予防剤、改善剤、緩和剤又は治療剤である、(1)に記載の調整剤。
(1) A regulator of the amount of transcobalamin II gene product, comprising 2-aminoethanesulfonic acid.
(2) The adjusting agent according to (1), which is a preventive agent, ameliorating agent, alleviating agent or therapeutic agent for a symptom and / or disease accompanied by a change in the amount of gene product of transcobalamin II.
本発明により、トランスコバラミンIIの遺伝子産物量を調整する試薬、医薬及び/又は食品を供給することが可能となった。さらには、トランスコバラミンIIの遺伝子発現量の変動を伴う症状及び/又は疾病に対する、副作用が少なく、長期間継続して服用しても安全な、予防剤、改善剤、緩和剤又は治療剤の提供が可能となった。 According to the present invention, it is possible to supply a reagent, a medicine and / or a food for adjusting the gene product amount of transcobalamin II. Furthermore, providing prophylactic, improving, alleviating or therapeutic agents that have few side effects and are safe to take for a long period of time for symptoms and / or diseases associated with fluctuations in the gene expression level of transcobalamin II Became possible.
本発明の実施の形態について以下に説明するが、本発明はこれに限定されるものではない。
本発明における「2−アミノエタンスルホン酸」としては、化学合成品のみでなく、魚の血合い部分、牡蠣や蜆などの貝類、イカ、タコなどの魚介類などから抽出した天然物由来の2−アミノエタンスルホン酸を用いることができる。
Embodiments of the present invention will be described below, but the present invention is not limited thereto.
The “2-aminoethanesulfonic acid” in the present invention is not only a chemically synthesized product but also a 2-amino acid derived from a natural product extracted from a bloody part of fish, shellfish such as oysters and sea bream, and seafood such as squid and octopus. Ethanesulfonic acid can be used.
本発明における「遺伝子産物」とは、転写産物又は翻訳産物のいずれでもよい。「転写産物」とは、遺伝子から転写の過程を経て生じる遺伝子、通常、RNAを示し、好ましくはmRNAを示す。「翻訳産物」とは、遺伝子から転写、翻訳の過程を得て生じるタンパク質を示し、未修飾であっても翻訳後修飾されていてもよい。 The “gene product” in the present invention may be either a transcription product or a translation product. “Transcription product” refers to a gene, usually RNA, preferably mRNA, which is produced from a gene through a transcription process. A “translation product” refers to a protein that is generated by a transcription and translation process from a gene, and may be unmodified or post-translationally modified.
本発明における「遺伝子」とは、細胞におけるDNA又はRNAのいずれもでもよく、ゲノムDNAのみならず、mRNA、aRNA、cRNA及びcDNAなども含むものであり、全長遺伝子のみでなく、その一部を含む遺伝子(expressed sequence tag:EST)などでもよい。 The “gene” in the present invention may be either DNA or RNA in a cell, and includes not only genomic DNA but also mRNA, aRNA, cRNA, cDNA and the like. It may be a gene containing an expressed sequence tag (EST).
通常、遺伝子産物量の分析は、当該遺伝子産物の転写産物又は翻訳産物の発現量を測定し、その発現量を補正し、その変動量を算出することにより可能である。遺伝子産物量を測定する方法としては、転写産物を検出し得るプローブやプライマーを用いる方法、翻訳産物を認識する抗体や結合する物質を用いる方法などがある。 Usually, the amount of gene product can be analyzed by measuring the expression level of the transcription product or translation product of the gene product, correcting the expression level, and calculating the amount of variation. Methods for measuring the amount of gene product include a method using a probe or primer that can detect a transcription product, a method using an antibody that recognizes a translation product, or a binding substance.
本発明の「トランスコバラミンII遺伝子産物量の調整剤」は、トランスコバラミンIIの遺伝子産物量(遺伝子発現量)を増加又は減少させることができる。 The “regulator of transcobalamin II gene product” according to the present invention can increase or decrease the amount of gene product (gene expression level) of transcobalamin II.
本発明の「トランスコバラミンII遺伝子産物量の調整剤」は、トランスコバラミンIIの遺伝子産物量を調整するための試薬や、これを含むキットとして提供することができる。 The “regulator of transcobalamin II gene product amount” of the present invention can be provided as a reagent for adjusting the gene product amount of transcobalamin II or a kit containing the same.
2−アミノエタンスルホン酸は固体でも液体でもよく、必要に応じて、pH調整剤、保存剤、防腐剤などを加えることもできる。試薬又はキットは、更に所望により、トランスコバラミンIIの遺伝子産物の発現量を解析するためのプライマー、プローブ、抗体などと組み合わせてもよい。 2-Aminoethanesulfonic acid may be solid or liquid, and a pH adjuster, preservative, preservative, etc. can be added as necessary. If desired, the reagent or kit may be further combined with a primer, a probe, an antibody, or the like for analyzing the expression level of the gene product of transcobalamin II.
試薬としての2−アミノエタンスルホン酸の使用量は、例えばマウスへ経口投与する場合、1日あたり50mg〜8000mg/kgであり、100mg〜6000mg/kgが好ましく、200mg〜4000mg/kgがより好ましい。1日量の2−アミノエタンスルホン酸を1日1回又は数回に分けて経口投与することができる。 The amount of 2-aminoethanesulfonic acid used as a reagent is, for example, 50 mg to 8000 mg / kg per day, preferably 100 mg to 6000 mg / kg, more preferably 200 mg to 4000 mg / kg when orally administered to mice. A daily dose of 2-aminoethanesulfonic acid can be orally administered once or several times daily.
また、本発明の「トランスコバラミンII遺伝子産物量の調整剤」は、2−アミノエタンスルホン酸を含有することを特徴とした経口用医薬及び/又は食品として提供することができる。また、トランスコバラミンII遺伝子産物量の変動は細胞内ビタミンB12濃度を変動させるので、「トランスコバラミンII遺伝子産物量の調整剤」は「細胞内ビタミンB12濃度の調整剤」としても使用可能である。
これらの経口用組成物には、2−アミノエタンスルホン酸の他、本発明の効果を損なわない範囲で、pH調整剤、保存剤、防腐剤、賦形剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味矯臭剤、清涼化剤、懸濁化剤、消泡剤、粘稠剤、溶解補助剤、界面活性剤、香料などを配合してもよい。さらに必要に応じて、常法により、錠剤、カプセル剤、散剤、顆粒剤、ドライシロップ剤などの経口用固形製剤又はドリンク剤などの内服液剤・飲料として提供することができる。
In addition, the “adjuster for the amount of transcobalamin II gene product” of the present invention can be provided as an oral medicine and / or food characterized by containing 2-aminoethanesulfonic acid. Further, since the change in the amount of transcobalamin II gene product changes the intracellular vitamin B12 concentration, the “regulator for transcobalamin II gene product amount” can also be used as the “regulator for intracellular vitamin B12 concentration”.
In addition to 2-aminoethanesulfonic acid, these oral compositions include pH adjusters, preservatives, preservatives, excipients, disintegrants, binders, lubricants, as long as the effects of the present invention are not impaired. Agents, antioxidants, coating agents, coloring agents, flavoring agents, cooling agents, suspending agents, antifoaming agents, thickening agents, solubilizing agents, surfactants, fragrances and the like may be added. Furthermore, if necessary, it can be provided as an oral liquid preparation / beverage such as a solid preparation for oral use such as tablets, capsules, powders, granules, dry syrups and the like, or a drink by a conventional method.
経口用組成物は、通常、効能・効果を標榜できる医薬品、医薬部外品や特定保健用食品などとして提供することができる。さらには、「トランスコバラミンII遺伝子産物量の調整剤」、「トランスコバラミンII異常を伴う症状や疾病の予防剤、改善剤、緩和剤又は治療剤」や「細胞内ビタミンB12濃度調整剤」などの表記を付して提供することも可能である。 Oral compositions can usually be provided as pharmaceuticals, quasi-drugs, foods for specified health use, etc. that can be used for their indications. Furthermore, “adjuster for transcobalamin II gene product”, “preventive agent, ameliorating agent, alleviating agent or therapeutic agent for symptoms and diseases accompanied by abnormal transcobalamin II”, “intracellular vitamin B12 concentration adjusting agent”, etc. It is also possible to provide it with a notation.
経口用組成物としての2−アミノエタンスルホン酸のヒト経口投与量は、年齢、性別、体重などを考慮して適宜増減できるが、通常、成人で1日あたり、500mg〜8000mgであり、1000mg〜6000mgが好ましく、3000mg〜4000mgがより好ましい。1日量の2−アミノエタンスルホン酸を1日1回又は数回に分けて経口投与することができる。 The human oral dosage of 2-aminoethanesulfonic acid as an oral composition can be appropriately increased or decreased in consideration of age, sex, weight, etc., but is usually 500 mg to 8000 mg per day for adults, and 1000 mg to 6000 mg is preferable, and 3000 mg to 4000 mg is more preferable. A daily dose of 2-aminoethanesulfonic acid can be orally administered once or several times daily.
本発明における「ビタミンB12」とは、天然型のヒドロキソコバラミン、シアノコバラミン等及び活性型のメチルコバラミン及びアデノシルコバラミン等であり、特に限定はされないが、好ましくは細胞内で機能するメチルコバラミン及びアデノシルコバラミンである。 “Vitamin B12” in the present invention includes natural hydroxocobalamin, cyanocobalamin and the like, and active methylcobalamin and adenosylcobalamin, and the like. Although not particularly limited, methylcobalamin and adenosyl that preferably function in cells are preferred. Cobalamin.
本発明における「トランスコバラミンII」とは、腎臓、肝臓などの全組織に存在し、組織細胞へのビタミンB12の輸送や腎臓での再吸収に関与しているタンパクであり、塩基配列や遺伝子情報なども解明されているタンパクである。 “Transcobalamin II” in the present invention is a protein that is present in all tissues such as kidney and liver and is involved in transport of vitamin B12 to tissue cells and reabsorption in the kidney. These are proteins that have been elucidated.
トランスコバラミンIIのタンパク情報、塩基配列情報及び遺伝子情報などは、欧州分子生物学研究所やHUGO遺伝子命名法委員会など公的機関やデータベースにより、容易に入手することができる。 Protein information, base sequence information, gene information, etc. of transcobalamin II can be easily obtained from public institutions and databases such as the European Institute for Molecular Biology and the HUGO Gene Nomenclature Committee.
トランスコバラミンIIの遺伝子情報およびタンパク情報を次に示す。
Approved Name /transcobalamin II
Approved Symbol /TCN2
HGNC ID/HGNC:11653
NUCLEOTIDE SEQUENCES/RefSeq:NM_000355
GENE RESOURCES/Entrez Gene:6948
PROTEIN RESOURCES/UniProtKB:P20062
The gene information and protein information of transcobalamin II are shown below.
Applied Name / transcobalamin II
Applied Symbol / TCN2
HGNC ID / HGNC: 11653
NUCLEOTIDE SEQUENCES / RefSeq: NM_000355
GENE RESOURCES / Entrez Gene: 6948
PROTEIN RESOURCES / UniProtKB: P20062
トランスコバラミンIIの遺伝子産物量(遺伝子発現量)の増加が認められる症状や疾病としては、2型子宮内膜腺癌、B細胞リンパ腫、C型肝炎、インフルエンザウイルス感染症、エイズウイルス感染症、エイズ関連カポジ肉腫、ヒト免疫不全ウイルス感染症、カポジ肉腫関連ヘルペスウイルス感染症、カルパイン3異常症、クローン病、ニューカッスル病ウイルス感染症、びまん性大細胞型B細胞リンパ腫、非気道熱傷、マラリア感染症、過敏性腸症候群、肝細胞癌、関節リウマチ、奇形精子症、気道熱傷、急性リンパ性白血病、急性拒絶反応、急性骨髄性白血病、急性前骨髄球性白血病、急性単芽球性白血病、単球性白血病、局所進行乳癌、結節性末梢性T細胞リンパ腫、結腸直腸腺癌、血管免疫芽球性T細胞性リンパ腫、甲状腺腺腫(濾胞腺腫)、甲状腺濾胞癌、硬化症、高悪性度前立腺上皮細胞内腫瘍、骨髄腫、脂肪腫、歯周炎、若年性特発性関節炎、若年性特発性関節炎、若年性皮膚筋炎、食道癌、食道扁平上皮癌、神経膠芽腫、腎癌、腎細胞癌、腎明細胞癌、髄膜炎、髄膜腫、星状細胞腫、節外性NK/T細胞リンパ腫、線維肉腫、前立腺肥大、多臓器不全、多嚢胞性卵巣症候群、多発性骨髄腫、単クローン性免疫グロブリン血症、敗血症ショック、肺炎、膿胸、肺腺癌、肺動脈性肺高血圧症、副腎皮質腺腫、平滑筋肉腫、慢性肉芽腫症、未分化大細胞リンパ腫、未分化肉腫、卵巣癌、卵巣腫瘍、卵巣腫瘍 類子宮内膜、類内膜癌、漿液性細胞腫、痙性対麻痺、胚細胞性腫瘍及び膵管腺癌などが挙げられる。 Symptoms and diseases in which the amount of transcobalamin II gene product (gene expression level) is increased include type 2 endometrial adenocarcinoma, B cell lymphoma, hepatitis C, influenza virus infection, AIDS virus infection, AIDS Related Kaposi's sarcoma, Human immunodeficiency virus infection, Kaposi's sarcoma-associated herpesvirus infection, Calpain 3 abnormality, Crohn's disease, Newcastle disease virus infection, Diffuse large B-cell lymphoma, Non-respiratory burn, Malaria infection, Irritable bowel syndrome, hepatocellular carcinoma, rheumatoid arthritis, teratospermia, airway burn, acute lymphoblastic leukemia, acute rejection, acute myeloid leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, monocytic Leukemia, locally advanced breast cancer, nodular peripheral T-cell lymphoma, colorectal adenocarcinoma, vascular immunoblastic T-cell lymphoma, thyroid adenoma (filter Adenoma), follicular thyroid cancer, sclerosis, high-grade prostate epithelial cell tumor, myeloma, lipoma, periodontitis, juvenile idiopathic arthritis, juvenile idiopathic arthritis, juvenile dermatomyositis, esophageal cancer, esophagus Squamous cell carcinoma, glioblastoma, renal cancer, renal cell carcinoma, clear cell carcinoma, meningitis, meningioma, astrocytoma, extranodal NK / T cell lymphoma, fibrosarcoma, prostatic hypertrophy, multiple Organ failure, polycystic ovary syndrome, multiple myeloma, monoclonal immunoglobulin, septic shock, pneumonia, empyema, lung adenocarcinoma, pulmonary arterial hypertension, adrenocortical adenoma, leiomyosarcoma, chronic granuloma Disease, anaplastic large cell lymphoma, anaplastic sarcoma, ovarian cancer, ovarian tumor, ovarian tumor, endometrium, endometrioid carcinoma, serous cell tumor, spastic paraplegia, germ cell tumor, pancreatic ductal adenocarcinoma, etc. It is done.
トランスコバラミンIIの遺伝子産物量(遺伝子発現量)の減少が認められる症状や疾病としては、1型子宮内膜腺癌、HIV感染症、T細胞性急性リンパ性白血病、X連鎖無ガンマグロブリン血症、エメリ・ドレフュス型筋ジストロフィー、コケイン症候群、てんかん、バーキットリンパ腫、ハンチントン病、非虚血性心筋症、メラノーマ、リンパ性白血病、悪性胸膜中皮腫、化膿性連鎖球菌、顔面肩甲上腕型筋ジストロフィー、筋萎縮性側索硬化症、結腸癌、結腸直腸癌、細胞傷害性肺癌、子宮頸癌、小細胞肺癌、心房細動、浸潤性食道扁平上皮腫、神経芽細胞腫、前駆Tリンパ芽球性白血病、前立腺癌、双極性障害、乳癌、乳腺癌、乳腺腫瘍、嚢胞性線維症、非小細胞肺癌、副腎皮質癌、分類不能型免疫不全症、慢性リンパ性白血病、慢性骨髄性白血病、未分化神経膠芽腫、扁平上皮癌、絨毛癌及び膵癌などが挙げられる。 Symptoms and diseases in which the amount of transcobalamin II gene product (gene expression level) is decreased include type 1 endometrial adenocarcinoma, HIV infection, T-cell acute lymphoblastic leukemia, X-linked agammaglobulinemia , Emery Dreyfus muscular dystrophy, Cocaine syndrome, epilepsy, Burkitt lymphoma, Huntington's disease, non-ischemic cardiomyopathy, melanoma, lymphocytic leukemia, malignant pleural mesothelioma, pyogenic streptococcus, facial scapulohumeral muscular dystrophy, muscle Amyotrophic lateral sclerosis, colon cancer, colorectal cancer, cytotoxic lung cancer, cervical cancer, small cell lung cancer, atrial fibrillation, invasive squamous cell carcinoma of the esophagus, neuroblastoma, progenitor T lymphoblastic leukemia , Prostate cancer, bipolar disorder, breast cancer, breast cancer, breast tumor, cystic fibrosis, non-small cell lung cancer, adrenocortical cancer, unclassifiable immunodeficiency, chronic lymphocytic leukemia, chronic Marrow leukemia, undifferentiated glioblastoma, squamous cell cancer, choriocarcinoma, and pancreatic cancer and the like.
従って、本発明の「トランスコバラミンII遺伝子産物量の調整剤」は、これらの症状や疾病を伴うトランスコバラミンIIの遺伝子産物量を調整することができる。さらには、「トランスコバラミンII遺伝子産物量の調整剤」の投与により、これらの症状や疾病を予防、改善、緩和及び/又は治療することが期待できる。 Therefore, the “adjuster for the amount of transcobalamin II gene product” of the present invention can adjust the amount of the gene product of transcobalamin II associated with these symptoms and diseases. Furthermore, it can be expected that these symptoms and diseases are prevented, ameliorated, alleviated and / or treated by administration of “adjuster for the amount of transcobalamin II gene product”.
本発明における「細胞」とは、ビタミンB12を代謝機能の一部に有する細胞であるか、トランスコバラミンIIの遺伝子産物を発現している細胞である。
細胞としては、例えば、血液細胞、肝細胞、腎細胞、筋細胞、神経細胞、グリア細胞、骨髄細胞、繊維芽細胞、繊維細胞、間質細胞、又はこれら細胞の前駆細胞、幹細胞もしくはガン細胞などが挙げられるが、これらに限定されるものではない。細胞は、好ましくは、血液細胞、筋細胞、肝細胞、又はそれらの前駆細胞もしくは幹細胞であり、ヒトを含む哺乳動物由来の細胞であることがより好ましい。
The “cell” in the present invention is a cell having vitamin B12 as a part of metabolic function, or a cell expressing the gene product of transcobalamin II.
Examples of cells include blood cells, hepatocytes, kidney cells, muscle cells, nerve cells, glial cells, bone marrow cells, fibroblasts, fiber cells, stromal cells, or precursor cells, stem cells, or cancer cells of these cells. However, it is not limited to these. The cells are preferably blood cells, muscle cells, hepatocytes, or precursor cells or stem cells thereof, and more preferably cells derived from mammals including humans.
以下の実施例により本発明を更に詳細に説明するが、本発明は実施例によって限定されるものではない。 The following examples further illustrate the present invention in detail but are not to be construed to limit the scope thereof.
試験例1:細胞におけるトランスコバラミンIIの遺伝子発現量に対する2−アミノエタンスルホン酸の調整作用
トランスコバラミンII遺伝子(Tcn2)の発現を変動させたマウス(Tcn2変動マウス)の血液細胞におけるトランスコバラミンIIの遺伝子発現量の変動を解析することにより、2−アミノエタンスルホン酸の調整作用を評価した。
Test Example 1: Modulating effect of 2-aminoethanesulfonic acid on the gene expression level of transcobalamin II in cells Transcobalamin II in blood cells of mice (Tcn2-variable mice) in which the expression of transcobalamin II gene (Tcn2) was varied By analyzing the variation of the gene expression level, the regulating action of 2-aminoethanesulfonic acid was evaluated.
実験動物には、7から11週齢のBALB/c系マウス、オス(日本エスエルシー(株))(12匹)を用いた。実験動物は入荷後、試験期間を通して標準飼料(オリエンタル酵母工業(株))及び滅菌水を自由に摂取させ、少なくとも1週間の馴化を行った。
実験群は、Tcn2変動マウス(4匹)、2−アミノエタンスルホン酸投与Tcn2変動マウス(薬剤投与Tcn2変動マウス)(4匹)及び健常マウス(4匹)とした。
As experimental animals, 7 to 11-week-old BALB / c mice, males (Japan SLC, Inc.) (12 animals) were used. After arrival, the laboratory animals were allowed to freely ingest standard feed (Oriental Yeast Co., Ltd.) and sterilized water throughout the test period and acclimated for at least one week.
The experimental groups were Tcn2 variable mice (4 mice), 2-aminoethanesulfonic acid-administered Tcn2 variable mice (drug-administered Tcn2 variable mice) (4 mice), and healthy mice (4 mice).
Tcn2変動マウスは、マウス・ラット用トレッドミル走行装置(バイオリサーチセンター(株))を用いた漸増的な強制走行負荷により作製した(走行条件:傾斜角度10度、走行開始速度9メートル/分、漸増ステップ3メートル/4分、52分間)。 Tcn2 variable mice were produced by gradually increasing forced running load using a treadmill running device for mice / rats (Bioresearch Center Co., Ltd.) (running conditions: inclination angle 10 degrees, running start speed 9 meters / minute, Incremental step 3 meters / 4 minutes, 52 minutes).
2−アミノエタンスルホン酸は、Tcn2の発現変動処置を施す前日まで2週間、1日1回、300mg/kgの投与量で経口投与し、処置終了直後にも経口投与した。 2-Aminoethanesulfonic acid was orally administered at a dose of 300 mg / kg once a day for 2 weeks until the day before the Tcn2 expression variation treatment was administered, and was also orally administered immediately after the end of the treatment.
細胞として血液細胞を選定した。動物からの血液細胞の採取は、Tcn2の発現変動処置の2時間後に深麻酔条件にてマウスを安楽死させ、腹部大静脈より血液を1mL採取し、ヌクレアーゼ不含水1mLを添加し、Isogen−LS(ニッポンジーン社)2mLを添加し、血液を溶解することにより行った。 Blood cells were selected as cells. Blood cells were collected from the animals by euthanizing the mice under deep anesthesia conditions 2 hours after the Tcn2 expression fluctuation treatment, collecting 1 mL of blood from the abdominal vena cava, adding 1 mL of nuclease-free water, and Isogen-LS. (Nippon Gene) 2 mL was added to dissolve the blood.
Isogen−LSに溶解された血液細胞からのRNAの粗抽出は、同試薬のプロトコールに従って実施した。粗抽出されたRNAは、RNeasy Mini Kit(Qiagen社)を用いてカラム精製を行った。
カラム精製後のTOTAL RNAに対して一旦定量とクオリティチェックを行った後、必要十分量のRNAから、血液に大量に含まれており、発現解析の妨げとなるグロビンmRNAの除去処理を行った後、再度、定量とクオリティチェックを実施した。グロビンmRNA除去処理にはGLOBINclear-Mouse/Rat (Ambion社)を用いた。
さらに、NanoDrop 1000 Spectrophotometer (Thermo Fisher Scientific社)を使用しtotal RNAの濃度を測定する。その後Agilent RNA 6000 Nano Kit(Agilent Technologies社)を使用し、Agilent 2100 Bioanalyzer(Agilent Technologies社)で電気泳動を行いtotal RNAのRIN値を測定した。
The crude extraction of RNA from blood cells dissolved in Isogen-LS was performed according to the protocol of the same reagent. The crudely extracted RNA was subjected to column purification using RNeasy Mini Kit (Qiagen).
After quantification and quality check of TOTAL RNA after column purification, after removal of globin mRNA that is contained in blood in large amounts from necessary and sufficient amount of RNA and hinders expression analysis Again, quantitative and quality checks were performed. For removing globin mRNA, GLOBINclear-Mouse / Rat (Ambion) was used.
Furthermore, the total RNA concentration is measured using NanoDrop 1000 Spectrophotometer (Thermo Fisher Scientific). Thereafter, electrophoresis was performed using Agilent RNA 6000 Nano Kit (Agilent Technologies) and Agilent 2100 Bioanalyzer (Agilent Technologies) to measure the RIN value of total RNA.
逆転写反応液を調製し、GeneAmp PCR System 9700(Life Technologies社)を用いて、RNAの逆転写反応を行った。
次に、BioMark 96.96 ダイナミックアレイの機器及び試薬添付のプロトコルに従い、Sample inletsにSample mixを、Assay inletsにAssay mixをアプライし、BioMarkによりリアルタイムPCR反応を行った。PCR反応回数は最大35サイクルとした。測定の反復回数は3回とした。
A reverse transcription reaction solution was prepared, and RNA reverse transcription reaction was performed using GeneAmp PCR System 9700 (Life Technologies).
Next, according to the BioMark 96.96 dynamic array device and the protocol attached to the reagent, Sample mix was applied to Sample mix, Assay mix was applied to Assay inlets, and real-time PCR reaction was performed using BioMark. The maximum number of PCR reactions was 35 cycles. The measurement was repeated three times.
トランスコバラミンII遺伝子(Tcn2)の発現量の比較は、リアルタイムPCRにより得られた一定の増幅産物量になるサイクル数(threshold cycle値:Ct値)から、βアクチン遺伝子(Actb)をそれぞれ内部標準遺伝子とし、基準となるサンプルの値を1.00とした時の相対値より算出し、健常マウスの血液細胞における遺伝子の発現量(平均値)を100%として算出した。
トランスコバラミンII遺伝子及びβアクチン遺伝子のPCRプライマーは、BioMark社より市販されているウェットバリデーションプライマーを用いた。
Comparison of the expression level of the transcobalamin II gene (Tcn2) is based on the number of cycles (threshold cycle value: Ct value) resulting in a constant amount of amplification product obtained by real-time PCR. And calculated from the relative value when the value of the reference sample is 1.00, and the gene expression level (average value) in the blood cells of healthy mice was calculated as 100%.
As PCR primers for the transcobalamin II gene and β-actin gene, wet validation primers commercially available from BioMark were used.
Tcn2変動マウス由来血液細胞におけるトランスコバラミンII遺伝子の発現量は、健常マウスと比較して著しく増加していた。
薬剤投与Tcn2変動マウスにおけるトランスコバラミンII遺伝子の発現量はTcn2変動マウスと比較して顕著に減少していた。
The expression level of the transcobalamin II gene in blood cells derived from Tcn2-variable mice was remarkably increased as compared with healthy mice.
The expression level of the transcobalamin II gene in the drug-administered Tcn2 variable mice was significantly reduced compared to the Tcn2 variable mice.
以上より、2−アミノエタンスルホン酸は、トランスコバラミンII遺伝子の発現量を調整することが明らかとなった。 From the above, it was revealed that 2-aminoethanesulfonic acid regulates the expression level of the transcobalamin II gene.
従って、トランスコバラミンII遺伝子の発現量を調整する試薬、医薬品、食品として、2−アミノエタンスルホン酸を提供することが可能となった。 Therefore, 2-aminoethanesulfonic acid can be provided as a reagent, pharmaceutical, or food for adjusting the expression level of the transcobalamin II gene.
本発明によりトランスコバラミンIIの遺伝子産物量を調整する試薬、医薬品及び/又は食品を提供することが可能となった。さらには、トランスコバラミンIIの遺伝子産物量(遺伝子発現量)の変動を伴う症状や疾病を予防、改善、緩和又は治療する経口用組成物を提供することが可能となった。 According to the present invention, it is possible to provide a reagent, a pharmaceutical product and / or a food product for adjusting the gene product amount of transcobalamin II. Furthermore, it has become possible to provide an oral composition for preventing, ameliorating, alleviating or treating symptoms and diseases associated with fluctuations in the amount of gene product (gene expression level) of transcobalamin II.
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012140308A JP6015158B2 (en) | 2012-06-22 | 2012-06-22 | Transcobalamin II gene product regulator |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012140308A JP6015158B2 (en) | 2012-06-22 | 2012-06-22 | Transcobalamin II gene product regulator |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014003919A true JP2014003919A (en) | 2014-01-16 |
JP6015158B2 JP6015158B2 (en) | 2016-10-26 |
Family
ID=50102300
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012140308A Active JP6015158B2 (en) | 2012-06-22 | 2012-06-22 | Transcobalamin II gene product regulator |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6015158B2 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004526793A (en) * | 2001-04-25 | 2004-09-02 | コバルツ リミテッド | Methods for treating or preventing functional vitamin B12 deficiency in an individual, and medical compositions for use in the methods |
JP2011021033A (en) * | 2010-10-29 | 2011-02-03 | Tsujido Chemical Corp | Anti-fatigue agent |
-
2012
- 2012-06-22 JP JP2012140308A patent/JP6015158B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004526793A (en) * | 2001-04-25 | 2004-09-02 | コバルツ リミテッド | Methods for treating or preventing functional vitamin B12 deficiency in an individual, and medical compositions for use in the methods |
JP2011021033A (en) * | 2010-10-29 | 2011-02-03 | Tsujido Chemical Corp | Anti-fatigue agent |
Also Published As
Publication number | Publication date |
---|---|
JP6015158B2 (en) | 2016-10-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Meltzer et al. | Clozapine-induced weight gain predicts improvement in psychopathology | |
JP4117901B2 (en) | A novel method of inhibiting reverse transcriptase-dependent virus replication by using inhibitors of deoxynucleotide synthesis | |
EP2953639B1 (en) | Treatment of dna damage and mitochondrial dysfunction using palm fruit juice | |
CN106554995B (en) | Method and kit for detecting gene related to tumor chemotherapy personalized medicine | |
CN109475644A (en) | Utilize the maintenance method and its utilization of the intracellular increased p53 level of platinum class anticancer agent induction | |
JP2016518816A (en) | Assays and methods for selecting treatment regimens for subjects suffering from depression | |
RU2728722C2 (en) | Intracellular atp increasing combination | |
JP6090836B2 (en) | Anti-tumor activity enhancer of chemotherapeutic agent | |
KR20180124055A (en) | Combination therapy for the treatment of acute myelogenous leukemia | |
JP2021530554A (en) | Methods and ACVR1 Inhibitors for Treatment of Diseases with Abnormal ACVR1 Expression | |
Kamatani et al. | Purine and pyrimidine metabolism | |
Liggett et al. | Precocious clonal hematopoiesis in Down syndrome is accompanied by immune dysregulation | |
CN113194963A (en) | Method for improving exercise tolerance of myalgic encephalomyelitis patient | |
JP6015158B2 (en) | Transcobalamin II gene product regulator | |
WO2022145439A1 (en) | Muscular atrophy inhibitor and method for inhibiting muscular atrophy | |
WO2013024865A1 (en) | Antitumor agent and therapeutic effect prediction method for patients with kras-mutated colorectal cancer | |
CN107205933A (en) | The combination of RAF inhibitor and AURORA kinase inhibitors | |
CN115992214A (en) | Use of a biomarker detection product in the preparation of a product for aiding in diagnosis, diagnosis or prognosis of a neural tube abnormality | |
US20200316067A1 (en) | Combination of raf inhibitors and taxanes | |
Salerno et al. | Effect of uridine administration to a patient with adenylosuccinate lyase deficiency | |
Fang et al. | Enzymatic-related network of catalysis, polyamine, and tumors for acetylpolyamine oxidase: from calculation to experiment | |
WO2022145438A1 (en) | PGC-1α EXPRESSION PROMOTING AGENT, MUSCLE-BUILDING AGENT, AND MITOCHONDRIA ACTIVATING AGENT | |
CN111228264A (en) | Application of combination of Sidapamide and CGB and autologous hematopoietic stem cells and combination drug | |
Nakagawara et al. | 5′-CMP and 5′-UMP alleviate dexamethasone-induced muscular atrophy in C2C12 myotubes | |
Ramalakshmi et al. | Cancer and oncogenes-An Overview |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150508 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160322 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160516 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160830 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160912 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6015158 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |