JP5045906B2 - 新規虚血マーカー及びこれを用いた虚血状態の検出方法 - Google Patents
新規虚血マーカー及びこれを用いた虚血状態の検出方法 Download PDFInfo
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- JP5045906B2 JP5045906B2 JP2007167761A JP2007167761A JP5045906B2 JP 5045906 B2 JP5045906 B2 JP 5045906B2 JP 2007167761 A JP2007167761 A JP 2007167761A JP 2007167761 A JP2007167761 A JP 2007167761A JP 5045906 B2 JP5045906 B2 JP 5045906B2
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Arpc3(actin related protein 2/3 complex,subunit 3),Pfn2(profilin 2),Sgce(sarcoglycan, epsilon),Actr3(ARP3 actin−related protein 3 homolog),H3f3b(H3 histone,amily 3B),Hist1h2bm(histone cluster 1,H2bm),Hist1h2bp(histone cluster 1,H2bp),Hist1h3a(histone cluster 1,H3a),Hist2h2aa1(histone cluster 2,H2aa1),Postn(periostin,osteoblast specific factor),Fbln5(fibulin 5),Col18a1(procollagen,type XVIII,alpha 1),Lamb1−1(laminin B1 subunit 1),Lamc1(laminin,gamma 1),Pros1(protein S alpha),Col6a2(procollagen,type VI,alpha 2),Ctnnb1(catenin[cadherin associated protein],beta 1),Dcbld2(discoidin,CUB and LCCL domain containing 2),Itga3(integrin alpha 3),Copb2(coatomer protein complex,subunit beta 2[beta prime]),Copa(coatomer protein complex subunit alpha),Cops3(COP9[constitutive photomorphogenic]homolog,subunit 3),Itm2b(integral membrane protein 2B),Aifm1(apoptosis−inducing factor,mitochondrion−associated 1),Trap1(TNF receptor−associated protein 1),Anxa4(annexin A4),Anxa6(annexin A6),Pla2g7(phospholipase A2,group VII[platelet−activating factor acetylhydrolase,plasma]),Aspn(asporin),Lox(lysyl oxidase),Crk(v−crk sarcoma virus CT10 oncogene homolog[avian]),Fbln1(fibulin 1),Gpr52(G protein−coupled receptor 52),Ppp2ca(protein phosphatase 2[formerly 2A],catalytic subunit,alpha isoform),Ppp2r2b(protein phosphatase 2[formerly 2A],regulatory subunit B[PR52],beta isoform),Lphn3(latrophilin 3),Ptprf(protein tyrosine phosphatase,receptor type,F),Rbbp9(retinoblastoma binding protein 9),Prrc1(proline−rich coiled−coil 1),Creg1(cellular repressor of E1A stimulated genes 1),Npm1(nucleophosmin 1),Rps4x(ribosomal protein S4,X−linked),Plrg1(pleiotropic regulator 1,PRL1 homolog[Arabidopsis]),Rnase4(ribonuclease,RNase A family 4),Ugp2(UDP−glucose pyrophosphorylase 2),Yars(tyrosyl−tRNA synthetase),Galnt10(UDP−N−acetyl−alpha−Dgalactosamine:polypeptide N−acetylgalactosaminyl transferase 10),Nudt21(nudix[nucleoside diphosphate linked moiety X]−type motif 21),Ube2l3(ubiquitin−conjugating enzyme E2L 3),Ufd1l(ubiquitin fusion degradation 1 like),Serpine1(serine[or cysteine]peptidase inhibitor,clade E,member 1[plasminogen activator inhibitor−1]),Uba52(ubiquitin A−52 residue ribosomal protein fusion product 1),Ube2v2(ubiquitin−conjugating enzyme E2 variant 2),Psma2(proteasome[prosome,macropain]subunit,alpha type 2),Psmb1(proteasome[prosome,macropain]subunit,beta type 1),Psmb4(proteasome[prosome,macropain]subunit,beta type 4),Psmb6(proteasome[prosome,macropain]subunit,beta type 6),Psmb7(proteasome[prosome,macropain]subunit,beta type 7),Try10(trypsin 10),Cct4(chaperonin subunit 4[delta]),Fkbp4(FK506 binding protein 4),Bmp1(bone morphogenetic protein 1),Hexb(hexosaminidase B),Glb1(galactosidase,beta 1),Aldh3a1(aldehyde dehydrogenase family 3,subfamily A1),Man2b2(mannosidase 2,alpha B2),Ngly1(N−glycanase 1),Fuca1(fucosidase,alpha−L−1,tissue),Oxct1(3−oxoacid CoA transferase 1),Nit2(nitrilase family,member 2),Loxl1(lysyl oxidase−like 1),Man1c1(mannosidase,alpha,class 1C,member 1),Crabp2(cellular retinoic acid binding protein II),Ctbs(chitobiase,di−N−acetyl−),Gsta4(glutathione S−transferase,alpha 4),Gstm2(glutathione S−transferase,mu 2),Hdhd2(haloacid dehalogenase−like hydrolase domain containing 2),Sgsh(N−sulfoglucosamine sulfohydrolase[sulfamidase]),Hyi(hydroxypyruvate isomerase homolog[E.coli]),Vasn(vasorin),Tfrc(transferrin receptor),Lcn2(lipocalin 2),Ap1m1(adaptor−related protein complex AP−1,mu subunit 1),C1qtnf6(C1q and tumor necrosis factor related protein 6),Vps26b(vacuolar protein sorting 26 homolog B[yeast]),Sec24d(SEC24 related gene family,member D[S.cerevisiae]),Slc44a2(solute carrier family 44,member 2),Cd14(CD14 antigen),Anpep(alanyl[membrane]aminopeptidase;CD13),Fkbp9(FK506 binding protein 9),Alcam(activated leukocyte cell adhesion molecule),C3(complement component 3),Tnc(tenascin C),Nudc(nuclear distribution gene C homolog[Aspergillus]),Sema4b(sema domain,immunoglobulin domain[Ig],transmembrane domain[TM]and short cytoplasmic domain,[semaphorin]4B),Agrin,Plxnb2(plexin B2),1110007L 15Rik(RIKEN cDNA 1110007L15 gene),2700085E 05Rik(RIKEN cDNA 2700085E05 gene),3110003A 17Rik(RIKEN cDNA 3110003A17 gene),4931406C 07Rik(RIKEN cDNA 4931406C07 gene),6530401N 04Rik(RIKEN cDNA 6530401N04 gene),EG54509(predicted gene,EG545091)
のうち少なくとも1つより選択されるタンパク質の発現レベル、好ましくはアポトーシス誘導因子(AIF)、骨形成タンパク質−1(BMP−1)、CD13、CD14、テネイシンC(TnC)、アグリンのうち少なくとも1つからなる虚血マーカータンパク質のタンパク質量を測定することを特徴とする、虚血状態の検出方法を提供する。組織が虚血−再灌流刺激を受けた際、それに対する応答としてこれまでに知られていなかった種々のタンパク質が細胞外・組織外に放出されることが、本発明者による培養心筋細胞での虚血/非虚血時発現タンパク質の網羅的解析から明らかとなった(図1)。これらのタンパク質を既存のデータベースと比較したところ、これまでに虚血マーカーとして報告のあるタンパク質とは異なり、アポトーシス、炎症反応、血管新生、細胞増殖、細胞接着や神経細胞再生などに関連する様々な機能を持ったタンパク質が特異的に発現していることが明らかとなった。虚血と結びついたそれぞれの反応において特異的に組織外に放出されるこれらのタンパク質の発現レベル、好ましくはこれらのタンパク質の試料中に含まれる量を測定することにより、虚血マーカーとして利用可能である。上記のマーカーは、これまでに機能が明らかにされてきたものの虚血との関連については明らかではないが、虚血後の再潅流時に放出されるものである。哺乳動物組織から採集される試料の種類、その採集方法、マーカータンパク質の検出方法などは当該分野で利用されるもののうちから適宜選択すればよいが、一般に再灌流後の血液を試料として採取するのが好ましい。また検出方法は何ら本発明を限定するものではないが、例えばヒト血液試料を採取し、血清中に含まれるタンパク質に対して上記マーカーに対する特異的抗体を用いたイムノアッセイ(簡便には蛍光イムノアッセイなど)やウェスタンブロッティングを行い、マーカータンパク質の存在を検出するといった方法があげられる。
Claims (5)
- 哺乳動物から採取した試料中に含まれるアグリンのタンパク質量を測定することを特徴とする哺乳動物組織における虚血状態の検出方法。
- 試料がヒト血清である、請求項1に記載の虚血状態検出方法。
- タンパク質量の測定が、抗原抗体反応を用いた測定である、請求項1又は2に記載の虚血状態検出方法。
- タンパク質量の測定が、予め測定された非虚血状態の試料中に含まれる前記マーカータンパク質の発現レベルとの比較工程を含む、請求項1〜3のいずれか1項に記載の虚血状態検出方法。
- 虚血が心臓虚血である、請求項1〜4のいずれか1項に記載の虚血状態検出方法。
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Cited By (1)
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US8545162B2 (en) | 2002-11-13 | 2013-10-01 | Skid Mor Development Llc | Material handling apparatus and method for operating |
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EP2425245B1 (en) * | 2009-04-27 | 2016-10-05 | Roche Diagnostics GmbH | Use of endostatin as a marker of heart failure |
JP5832534B2 (ja) * | 2010-07-28 | 2015-12-16 | アボット ゲーエムベーハー ウント コー. カーゲー | 虚血性脳卒中を検出する方法 |
US20130236917A1 (en) * | 2010-11-12 | 2013-09-12 | The Johns Hopkins University | Albumin-bound protein/peptide complex as a biomarker for disease |
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