KR102455071B1 - Composition for regulating AQP4 expression or activation comprising L-theanine - Google Patents
Composition for regulating AQP4 expression or activation comprising L-theanine Download PDFInfo
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Abstract
본 발명은 L-테아닌 (L-theanine)을 유효성분으로 함유하며, 뇌세포의 AQP4 (Aquaporin 4) 발현 또는 활성 조절용 조성물에 관한 것으로, 보다 상세하게는 인슐린 및 β-아밀로이드가 처리된 세포에서 AQP4, GFAP, BDNF, LRP1, MMP-2 및 MMP-9의 단백질 발현이 감소가 확인되었으나, L-테아닌의 처리 농도가 증가함에 따라 성상세포(astrocytic) 특성을 나타내는 AQP4의 발현을 증가시켰으며, 노화(aging) 회복과 관련된 GFAP 및 BDNF의 발현이 증가시키고, β-아밀로이드 축적을 억제시키는 LRP1, MMP-2 및 MMP-9의 발현을 증가시키는 것으로 확인됨에 따라, 상기 L-테아닌을 유효성분으로 함유하는 조성물은 AQP4 발현 조절용 조성물로 제공될 수 있다.The present invention relates to a composition for regulating the expression or activity of AQP4 (Aquaporin 4) in brain cells containing L-theanine as an active ingredient, and more particularly, AQP4 in cells treated with insulin and β-amyloid , GFAP, BDNF, LRP1, MMP-2 and MMP-9 protein expression was confirmed to decrease, but as the treatment concentration of L-theanine increased, the expression of AQP4, which exhibits astrocytic characteristics, was increased, and aging (aging) As it was confirmed to increase the expression of GFAP and BDNF related to recovery and increase the expression of LRP1, MMP-2 and MMP-9, which inhibit β-amyloid accumulation, the L-theanine is contained as an active ingredient The composition may be provided as a composition for regulating AQP4 expression.
Description
본 발명은 L-테아닌 (L-theanine)을 유효성분으로 함유하며, 뇌세포의 AQP4 (Aquaporin 4) 발현 또는 활성 조절용 조성물에 관한 것이다.The present invention contains L-theanine as an active ingredient, and relates to a composition for regulating the expression or activity of AQP4 (Aquaporin 4) in brain cells.
성상세포(astrocyte)는 뻗어 있는 많은 돌기 때문에 별처럼 보이는 신경 아교 세포로 뇌와 척수에 존재하여, 혈뇌장벽(혈액-뇌 장벽)의 안쪽 세포들을 생화학적으로 도와주는 역할을 하며 혈관벽에 돌기가 붙어 있어 신경세포에 영양분을 공급하는 역할을 한다. 그 밖에도 신경세포의 이온농도 조절, 신경세포의 지지, 노폐물의 제거, 식세포 작용 등의 다양한 역할을 수행한다. 또한 신경조직이 손상되면 신경교종이라는 돌기로 증식하여 그 부분을 채우기도 하며 손상된 조직을 복구하거나 파괴하는 역할을 한다. 또한, 성상세포는 베타 아밀로이드 축적을 제어하여 알츠하이머병(Alzheimer’s disease)나 파킨슨병(Parkinson’s disease)를 제어하는 역할을 수행하며, 성상세포에서 베타 아밀로이드의 축적 제어가 되지 않는다면 퇴행성 뇌질환이 발생될 수 있다.Astrocytes are glial cells that look like stars because of the many protrusions that extend and exist in the brain and spinal cord. It serves to supply nutrients to nerve cells. In addition, it performs various roles such as regulating the concentration of ions in nerve cells, supporting nerve cells, removing wastes, and phagocytosis. In addition, when the nerve tissue is damaged, it proliferates with a protrusion called a glioma and fills that part, and plays a role in repairing or destroying the damaged tissue. In addition, astrocytes play a role in controlling the accumulation of beta-amyloid to control Alzheimer's disease or Parkinson's disease, and if the accumulation of beta-amyloid in astrocytes is not controlled, degenerative brain disease may occur. have.
퇴행성 뇌질환으로 알츠하이머병, 파킨슨병 등이 대표적이며 특히 알츠하이머병의 병변으로 뇌에서의 베타 아밀로이드의 축적과 타우 단백질(Tau protein)의 인산화가 알려져 있다. 정상적인 뇌는 베타 아밀로이드의 축적을 방지하기 위해 베타 아밀로이드 분해효소(β-amyloid degradation enzyme)의 활성화를 통해 조절한다.As degenerative brain diseases, Alzheimer's disease and Parkinson's disease are representative. In particular, the accumulation of beta-amyloid in the brain and phosphorylation of Tau protein are known as lesions of Alzheimer's disease. In the normal brain, it is regulated through the activation of β-amyloid degradation enzyme to prevent the accumulation of β-amyloid.
아쿠아포린-4(aquaporin-4, AQP4)는 물 수송 막단백질로 알려져 있으며, 최근 연구에 의하면 성상 세포의 막단백질로써 베타 아밀로이드의 제거 또는 글루타메이트의 흡수에 기여하여 신경세포를 보호하는 것으로 확인되었다. 성상세포가 손상된 신경세포를 복구시키고 새로운 신경세포를 생성한다는 것이 밝혀져 in vivo 연구에서 치매, 뇌졸중 후유증 등의 뇌 손상에 대한 AQP4의 역할 연구가 활발히 이루어지고 있으나, 이는 성상세포 기반 AQP4의 역할로 알려져 있으며 in vitro 연구에서 신경교종세포 (glioma cell)에서의 AQP4의 역할 및 발현 여부는 불분명하다.Aquaporin-4 (aquaporin-4, AQP4) is known as a water transport membrane protein, and recent studies have confirmed that it is a membrane protein of astrocytes and contributes to the removal of beta-amyloid or absorption of glutamate to protect nerve cells. As it was found that astrocytes repair damaged nerve cells and generate new nerve cells, studies on the role of AQP4 in brain damage such as dementia and stroke sequelae are being actively conducted in in vivo studies, but this is known as the role of astrocyte-based AQP4. and the role and expression of AQP4 in glioma cells in in vitro studies is unclear.
본 발명은 시험관 내(in vitro)에서 뇌세포의 AQP4 (Aquaporin 4) 발현 또는 활성을 조절하기 위해 L-테아닌 (L-theanine)을 유효성분으로 함유하는 AQP4 발현 조절용 조성물을 제공하고자 한다.An object of the present invention is to provide a composition for regulating AQP4 expression containing L-theanine as an active ingredient in order to regulate the expression or activity of AQP4 (Aquaporin 4) in brain cells in vitro.
본 발명은 L-테아닌 (L-theanine)을 유효성분으로 함유하며, 시험관 내(in vitro)에서 뇌세포의 AQP4 (Aquaporin 4) 발현 또는 활성 조절용 시약조성물을 제공한다.The present invention provides a reagent composition for regulating the expression or activity of AQP4 (Aquaporin 4) in brain cells in vitro, containing L-theanine as an active ingredient.
본 발명은 개체로부터 분리된 뇌세포를 계대배양하여 노화를 유도하는 단계; The present invention includes the steps of inducing aging by subculture of brain cells isolated from the subject;
상기 노화가 유도된 뇌세포에 인슐린 및 β-아밀로이드로 이루어진 군에서 선택되는 하나 이상을 처리하여 뇌세포 손상을 유도하는 단계; Inducing brain cell damage by treating the aging-induced brain cells with at least one selected from the group consisting of insulin and β-amyloid;
상기 손상된 뇌세포에 L-테아닌을 처리하는 단계를 포함하는 AQP4 발현 조절방법을 제공한다.It provides a method for regulating AQP4 expression comprising the step of treating the damaged brain cells with L-theanine.
본 발명에 따르면, 인슐린 및 β-아밀로이드가 처리된 세포에서 AQP4, GFAP, BDNF, LRP1, MMP-2 및 MMP-9의 단백질 발현이 감소가 확인되었으나, L-테아닌의 처리 농도가 증가함에 따라 성상세포(astrocytic) 특성을 나타내는 AQP4의 발현을 증가시켰으며, 노화(aging) 회복과 관련된 GFAP 및 BDNF의 발현이 증가시키고, β-아밀로이드 축적을 억제시키는 LRP1, MMP-2 및 MMP-9의 발현을 증가시키는 것으로 확인됨에 따라, 상기 L-테아닌을 유효성분으로 함유하는 조성물은 AQP4 발현 조절용 조성물로 제공될 수 있다.According to the present invention, it was confirmed that the protein expression of AQP4, GFAP, BDNF, LRP1, MMP-2 and MMP-9 was decreased in the cells treated with insulin and β-amyloid, but as the treatment concentration of L-theanine increased, the properties It increased the expression of AQP4 indicating astrocytic properties, increased the expression of GFAP and BDNF associated with aging recovery, and suppressed the expression of LRP1, MMP-2 and MMP-9, which inhibit β-amyloid accumulation. As confirmed to increase, the composition containing L-theanine as an active ingredient may be provided as a composition for regulating AQP4 expression.
도 1은 계대배양으로 노화가 유도된 C6 세포 (cell passage 75)에서 L-테아닌 (L-theanine) 처리에 따른 세포 생존율을 확인한 MTT 분석 결과이다.
도 2는 계대배양으로 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 세포손상이 유도된 C6 세포에서 L-테아닌 (L-theanine) 처리에 따른 세포 생존율을 확인한 MTT 분석 결과이다.
도 3은 계대배양으로 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 세포손상이 유도된 C6 세포에서 L-테아닌 (L-theanine) 처리에 따른 AQP4, GFAP, BDNF, LRP1, MMP-2 및 MMP-9의 발현 수준을 확인한 웨스턴 블롯 분석 결과이다.
도 4는 계대배양으로 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 세포손상이 유도된 C6 세포에서 L-테아닌 (L-theanine) 처리에 따른 글루타메이트 흡수율을 확인한 결과이다.1 is an MTT analysis result confirming the cell viability according to the treatment with L-theanine (L-theanine) in C6 cells (cell passage 75) induced senescence by subculture.
2 is an MTT analysis result confirming cell viability according to L-theanine treatment in C6 cells in which senescence is induced by subculture and cell damage is induced by insulin and β-amyloid.
Figure 3 is AQP4, GFAP, BDNF, LRP1, MMP-2 and MMP- according to L-theanine treatment in C6 cells induced senescence by subculture and cell damage induced by insulin and β-amyloid; 9 is the result of Western blot analysis confirming the expression level.
Figure 4 is the result of confirming the glutamate absorption rate according to the L-theanine (L-theanine) treatment in C6 cells induced senescence by subculture and cell damage induced by insulin and β- amyloid.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 L-테아닌 (L-theanine)을 유효성분으로 함유하며, 시험관 내(in vitro)에서 뇌세포의 AQP4 (Aquaporin 4) 발현 또는 활성 증가용 시약조성물을 제공할 수 있다.The present invention can provide a reagent composition containing L-theanine as an active ingredient and for increasing the expression or activity of AQP4 (Aquaporin 4) in brain cells in vitro.
상기 L-테아닌은 계대배양에 의해 노화되고, 인슐린 및 β-아밀로이드로 이루어진 군에서 선택되는 하나 이상에 의해 손상된 뇌세포의 AQP4 발현 또는 활성을 증가시키는 것일 수 있다.The L-theanine may increase the expression or activity of AQP4 in brain cells aged by subculture and damaged by one or more selected from the group consisting of insulin and β-amyloid.
상기 뇌세포는 성상세포 및 신경교종세포로 이루어진 군에서 선택되는 것일 수 있다.The brain cells may be selected from the group consisting of astrocytes and glioma cells.
상기 L-테아닌은 손상된 뇌세포에서 GFAP, BNDF, LRP1, MMP-2 및 MMP-9로 이루어진 군에서 선택되는 하나 이상의 발현 또는 활성을 추가로 더 증가시키는 것일 수 있다.The L-theanine may further increase the expression or activity of one or more selected from the group consisting of GFAP, BNDF, LRP1, MMP-2 and MMP-9 in damaged brain cells.
또한, 본 발명은 개체로부터 분리된 뇌세포를 계대배양하여 노화를 유도하는 단계; 상기 노화가 유도된 뇌세포에 인슐린 및 β-아밀로이드로 이루어진 군에서 선택되는 하나 이상을 처리하여 뇌세포 손상을 유도하는 단계; 및In addition, the present invention includes the steps of inducing aging by subculture of brain cells isolated from the subject; Inducing brain cell damage by treating the aging-induced brain cells with at least one selected from the group consisting of insulin and β-amyloid; and
상기 손상된 뇌세포에 L-테아닌을 처리하는 단계를 포함하는 AQP4 발현 조절방법을 제공할 수 있다.It is possible to provide a method for regulating AQP4 expression comprising the step of treating the damaged brain cells with L-theanine.
상기 L-테아닌은 손상된 뇌세포의 AQP4 발현을 증가시키는 것일 수 있다.The L-theanine may increase the expression of AQP4 in damaged brain cells.
상기 L-테아닌은 손상된 뇌세포에서 GFAP, BNDF, LRP1, MMP-2 및 MMP-9로 이루어진 군에서 선택되는 하나 이상의 발현을 추가로 더 증가시키는 것일 수 있다.The L-theanine may further increase the expression of one or more selected from the group consisting of GFAP, BNDF, LRP1, MMP-2 and MMP-9 in damaged brain cells.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, to help the understanding of the present invention, examples will be described in detail. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.
<참고예><Reference example>
하기의 참고예들은 본 발명에 따른 각각의 실시예에 공통적으로 적용되는 참고예를 제공하기 위한 것이다.The following reference examples are intended to provide reference examples commonly applied to each embodiment according to the present invention.
1. 응집된 β-아밀로이드 준비1. Aggregated β-Amyloid Preparation
β-아밀로이드 (β-amyloid; Abcam, ab120301)를 250 μM로 제조하여 37℃의 조건에서 3일간 방치하여 응집(aggregation)을 유도하여 사용하였다.β-amyloid (β-amyloid; Abcam, ab120301) was prepared at 250 μM and left at 37° C. for 3 days to induce aggregation.
2. 세포 배양2. Cell Culture
C6 세포 (ATCC, CCL-107)를 DMEM (with FBS, antibiotics)에 37℃, 5% CO2 조건에서 배양하여 사용하였으며, 모든 실험에서 cell passage는 #75로 고정하였다.C6 cells (ATCC, CCL-107) were cultured in DMEM (with FBS, antibiotics) at 37° C., 5% CO 2 conditions, and cell passage was fixed at #75 in all experiments.
<실시예 1> 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 손상된 C6 세포에서 L-테아닌 처리에 따른 세포 생존도 확인<Example 1> Confirmation of cell viability according to L-theanine treatment in C6 cells induced senescence and damaged by insulin and β-amyloid
먼저, 계대배양에 의해 노화가 유도된 C6 세포 (cell passage 75, 5×104 cells/well)를 96-웰 세포 배양 플레이트에 분주하고 24시간 배양한 후 L-테아닌을 10, 50, 100, 250 및 500 μg/ml 농도로 처리하여 48시간 배양하였다. 상기 배양된 C6 세포에 MTT 용액 (final concentration: 500 μg/ml)를 각 well에 처리하여 4시간 반응시키고 상등액을 제거한 후 DMSO로 생성된 포르마잔을 용해시키고 ELISA reader 기기를 이용하여 550 nm 파장에서의 흡광도를 측정하여 세포 생존도를 확인하였다.First, senescence-induced C6 cells (cell passage 75, 5×10 4 cells/well) by subculture were dispensed in a 96-well cell culture plate and cultured for 24 hours, followed by 10, 50, 100, L-theanine. Treated with 250 and 500 μg / ml concentration and incubated for 48 hours. The cultured C6 cells were treated with MTT solution (final concentration: 500 μg/ml) in each well and reacted for 4 hours. After removing the supernatant, the formazan generated with DMSO was dissolved and ELISA reader at a wavelength of 550 nm. Cell viability was confirmed by measuring the absorbance.
그 결과, 도 1과 같이 L-테아닌은 C6 세포의 세포사멸을 유도하지 않는 것이 확인되었다.As a result, as shown in FIG. 1 , it was confirmed that L-theanine did not induce apoptosis of C6 cells.
다음으로 계대배양에 의해 노화가 유도된 C6 세포 (5×104 cells/well)를 96-웰 세포 배양 플레이트에 분주하고 24시간 배양한 후 인슐린 (100 μg/ml)과 β-아밀로이드 (5 μM)를 각각 또는 병용 처리하여 48시간 배양하였으며, L-테아닌을 10, 50, 100, 250 및 500 μg/ml 농도로 β-아밀로이드와 함께 처리하였다. 이후 앞선 실험과 동일한 방법으로 MTT 분석을 수행하여 세포 생존도를 확인하였다.Next, senescence-induced C6 cells (5×10 4 cells/well) by subculture were dispensed in a 96-well cell culture plate and cultured for 24 hours, followed by insulin (100 μg/ml) and β-amyloid (5 μM). ) were treated individually or in combination and cultured for 48 hours, and L-theanine was treated with β-amyloid at concentrations of 10, 50, 100, 250 and 500 μg/ml. Thereafter, MTT analysis was performed in the same manner as in the previous experiment to confirm cell viability.
그 결과, 도 2와 같이 인슐린 단독 처리군과 비교하여 인슐린과 β-아밀로이드 병용 처리군의 세포사멸에 증가되었으며, 인슐린 단독 처리군 및 인슐린과 β-아밀로이드 병용 처리군 모두 L-테아닌의 농도의존적으로 세포 생존율이 증가하는 것을 확인할 수 있었다 (100 μg/ml의 L-theanine 처리군 간 비교; 74.29%, 67.11%). As a result, as shown in FIG. 2 , the apoptosis of the insulin and β-amyloid combination treatment group was increased compared to the insulin alone treatment group, and both the insulin alone treatment group and the insulin and β-amyloid combination treatment group were L-theanine concentration-dependently. It was confirmed that the cell viability increased (comparison between groups treated with 100 μg/ml of L-theanine; 74.29%, 67.11%).
<실시예 2> 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 손상된 C6 세포에서 L-테아닌 처리에 따른 단백질 발현 수준 확인<Example 2> Confirmation of protein expression level according to L-theanine treatment in C6 cells induced senescence and damaged by insulin and β-amyloid
계대배양에 의해 노화가 유도된 C6 세포 (1×105 cells/well)를 6-웰 플레이트에 분주하여 24시간 배양한 후 인슐린 (100 μg/ml)과 β-아밀로이드 (5 μM)를 단독 또는 병용 처리하였으며, L-테아닌을 10, 50, 100, 250 및 500 μg/ml 농도로 함께 처리하여 48시간 동안 배양하였다. 배양 후 AQP4, GFAP, BNDF, LRP1, MMP-2 및 MMP-9의 발현을 확인하기 위해 웨스턴 블롯을 수행하였다.C6 cells induced senescence by subculture (1×10 5 cells/well) were dispensed in a 6-well plate and cultured for 24 hours, followed by insulin (100 μg/ml) and β-amyloid (5 μM) alone or Co-treatment was performed, and L-theanine was treated with 10, 50, 100, 250 and 500 μg/ml concentrations and cultured for 48 hours. After culture, Western blot was performed to confirm the expression of AQP4, GFAP, BNDF, LRP1, MMP-2 and MMP-9.
ThermoFisher Scientific 사의 Mem-PER™ Plus Membrane Protein Extraction Kit를 사용하여 AQP4 및 LRP1의 발현(100 μg)을 확인하였으며, RIPA lysis buffer로 전체 단백질을 추출하여 GFAP, BDNF, MMP-2 및 MMP-9의 발현(50 μg)을 확인하였다. 단백질의 정량은 BCA assay로 확인하였으며 degradation된 단백질을 10% polyacrylamide gel에 loading 하였다(120 V, 1시간). PVDF membrane에 transfer (100V, 1시간)하고 3% skim milk solution에 blocking한 후, AQP4 (cell signaling, #59678, 1:500 dilution), GFAP (cell signaling, #80788, 1:500 dilution), BDNF (Abcam, ab108319, 1:500 dilution), LRP1 (cell signaling, #64099, 1:500 dilution), MMP-2 (Abcam, ab86607, 1: 500 dilution), MMP-9 (Abcam, ab38898, 1:500 dilution), β-actin (cell signaling, #3700, 1:1000 dilution)에 하루 동안 반응시켰다. TBS-T solution으로 3회 washing하고 secondary antibody (rabbit, cell signaling, #7074, 1:5,000 dilution) 또는 secondary antibody (mouse, cell singaling, #7076, 1:5,000 dilution)에 1시간, 상온에서 반응시키고 TBS-T solution으로 3회 세척하였다. ThermoFisher scientific 사의 SuperSignal Chemiluminescent Substrates를 선반응시키고 Chemidoc (UVP Vision Works® LS Image Acquisition & Analysis Software, Upland, CA)으로 단백질의 발현을 정성 및 정량하여 확인하였다.The expression of AQP4 and LRP1 (100 μg) was confirmed using ThermoFisher Scientific's Mem-PER™ Plus Membrane Protein Extraction Kit, and the expression of GFAP, BDNF, MMP-2 and MMP-9 was extracted by extracting the entire protein with RIPA lysis buffer. (50 μg) was confirmed. Protein quantification was confirmed by BCA assay, and the degraded protein was loaded on 10% polyacrylamide gel (120 V, 1 hour). After transfer to PVDF membrane (100V, 1 hour) and blocking in 3% skim milk solution, AQP4 (cell signaling, #59678, 1:500 dilution), GFAP (cell signaling, #80788, 1:500 dilution), BDNF (Abcam, ab108319, 1:500 dilution), LRP1 (cell signaling, #64099, 1:500 dilution), MMP-2 (Abcam, ab86607, 1:500 dilution), MMP-9 (Abcam, ab38898, 1:500) dilution) and β-actin (cell signaling, #3700, 1:1000 dilution) for one day. Wash 3 times with TBS-T solution and react with secondary antibody (rabbit, cell signaling, #7074, 1:5,000 dilution) or secondary antibody (mouse, cell singaling, #7076, 1:5,000 dilution) for 1 hour at room temperature Washed 3 times with TBS-T solution. ThermoFisher scientific's SuperSignal Chemiluminescent Substrates were pre-reacted, and protein expression was confirmed by qualitative and quantitative analysis using Chemidoc (UVP Vision Works ® LS Image Acquisition & Analysis Software, Upland, CA).
그 결과, 도 3과 같이 인슐린 단독 처리군과 인슐린 및 β-아밀로이드 병용 처리군에서 AQP4, GFAP, BDNF, LRP1, MMP-2 및 MMP-9의 단백질 발현이 감소가 확인되었으며, 특히 병용 처리군에서 발현 감소가 매우 뚜렷하게 확인되었으나, L-테아닌의 처리 농도가 증가함에 따라 성상세포(astrocytic) 특성 및 노화(aging) 회복과 관련된 AQP4, GFAP 및 BDNF의 발현이 증가하는 것을 확인할 수 있었으며, β-아밀로이드 축적을 억제시키는 LRP1, MMP-2 및 MMP-9의 발현 증가를 확인할 수 있었다.As a result, as shown in Figure 3, it was confirmed that the protein expression of AQP4, GFAP, BDNF, LRP1, MMP-2 and MMP-9 was decreased in the insulin-only treatment group and the insulin and β-amyloid combination treatment group, especially in the combination treatment group Although the decrease in expression was very clearly confirmed, as the treatment concentration of L-theanine increased, it was confirmed that the expression of AQP4, GFAP and BDNF related to astrocytic characteristics and aging recovery increased, and β-amyloid It was confirmed that the expression of LRP1, MMP-2 and MMP-9, which inhibits accumulation, is increased.
<실시예 3> 노화가 유도되고 인슐린 및 β-아밀로이드에 의해 손상된 C6 세포에서 L-테아닌 처리에 따른 글루타메이트 흡수율 (glutamate uptake) 확인<Example 3> Confirmation of glutamate uptake according to L-theanine treatment in C6 cells induced senescence and damaged by insulin and β-amyloid
계대배양에 의해 노화가 유도된 C6 세포 (1×105 cells/well)를 6-웰 플레이트에 분주하여 24시간 배양한 후 인슐린 (100 μg/ml)과 β-아밀로이드 (5 μM)를 단독 또는 병용 처리하였으며, L-테아닌을 10, 50, 100, 250 및 500 μg/ml 농도로 함께 처리하여 48시간 동안 배양하였다.C6 cells induced senescence by subculture (1×10 5 cells/well) were dispensed in a 6-well plate and cultured for 24 hours, followed by insulin (100 μg/ml) and β-amyloid (5 μM) alone or Co-treatment was performed, and L-theanine was treated with 10, 50, 100, 250 and 500 μg/ml concentrations and cultured for 48 hours.
배양된 세포를 용해시킨 후, 13,000 rpm, 10분간 원심분리하여 불순물을 제거하고 제조사의 설명서를 참고하여 Glutamate-Glo™ Assay를 수행하였으며, GloMax luminescence (GM3510)의 기기로 인광광도를 측정하여 글루타메이트 흡수율을 확인하였다.After lysing the cultured cells, the impurities were removed by centrifugation at 13,000 rpm for 10 minutes, and the Glutamate-Glo™ Assay was performed referring to the manufacturer's instructions. was confirmed.
그 결과, 도 4와 같이 인슐린 또는 β-아밀로이드 단독 처리군에서 글루타메이트 흡수 감소가 확인되었으며, 인슐린 및 β-아밀로이드 병용 처리군에서는 글루타메이트 흡수 감소 비율이 더욱 증가되는 것이 확인됨에 따라 세포손상이 더욱 심화되는 것을 확인할 수 있었다. 그러나 L-테아닌 처리 농도 증가에 따라 인슐린 및 β-아밀로이드 병용 처리군의 글루타메이트 흡수율이 증가되는 것을 확인할 수 있었다 (100 μg/ml의 L-theanine 처리군 간 비교; 62.74%, 56.15%).As a result, as shown in FIG. 4 , a decrease in glutamate absorption was confirmed in the group treated with insulin or β-amyloid alone, and it was confirmed that the decreased rate of glutamate absorption was further increased in the group treated with insulin and β-amyloid. could confirm that However, it was confirmed that the glutamate absorption rate of the insulin and β-amyloid combination treatment group increased as the L-theanine treatment concentration increased (comparison between the L-theanine treatment groups at 100 μg/ml; 62.74%, 56.15%).
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As described above in detail a specific part of the content of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (7)
상기 노화가 유도된 뇌세포에 인슐린 및 β-아밀로이드로 이루어진 군에서 선택되는 하나 이상을 처리하여 뇌세포 손상을 유도하는 단계;
상기 손상된 뇌세포에 L-테아닌을 처리하는 단계를 포함하는 AQP4 발현 조절방법.Inducing aging by sub-culturing brain cells isolated from the subject;
Inducing brain cell damage by treating the aging-induced brain cells with one or more selected from the group consisting of insulin and β-amyloid;
A method for regulating AQP4 expression comprising the step of treating the damaged brain cells with L-theanine.
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