사하와 락타시스틴 병합처치에 의한 망막색소상피세포에서의 아폽토시스 연구

• 영문명: RPE Cell Apoptosis by the Combination Treatment of SAHA and Lactacystin
• 발행기관: 대한안과학회
• 저자명: 김태현 박찬수 노지현 유경원 안희배 박우찬 서수영 노세현,Tae Hyun Kim, M.D., Chan Soo Park, M.D., Jee Hyun Rho, M.D., Kyung Won Yoo, M.D., Hee Bae Ahn, M.D., Woo Chan Park, M.D., Su Young Seo, M.D., Sae Hyun Rho, M.D.
• 간행물 정보: 『대한안과학회지』Ophthalmological Society,volume48,number4, 563~572쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2007.04.30

영문 초록

Purpose: To establish a new therapeutic strategy for proliferative vitreoretinopathhy (PVR), we examined the effect of combined treatment with HDAC inhibitor SAHA and proteasome inhibitor lactacystin in human retinal pigment epithelial (RPE) cells, ARPE-19. Methods: Viability was determined by trypan blue exclusion assay. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Proteasome activity was measured by fluorophotometry. The expression and degradation of apoptosis-related proteins were assesssed by Western blotting. Subcellular location of apoptosis-related factors was monitored by confocal miscroscopy. Results: A single treatment with 5 ?M SAHA or 10 ?M lactacystin did not reduce cell viability. However, combination treatment with 5 ?M SAHA and 10 ?M lactacystin substantially reduced the viability, because the mixture induced the reduction of MMP and nuclear condensation or fragmentation. Moreover, the combination treatment triggered the activation of caspase-3 and the production of PARP cleavage products. These data indicate that the combination treatment efficiently induces apoptosis in ARPE-19 cells. However, co-treatment of SAHA did not augment the proteasome inhibitory activity of lactacystin, nor did co-treatment of lactacystin augment acetylation of histones. It is notable that while p53 and CAD were observed in the mitochondria of cells treated with SAHA, they were translocated into the nucleus after the combination treatment. Conclusions: These results suggest that the combination treatment of SAHA and lactacystin effectively induced apoptosis in ARPE-19 cells. Further work is warranted to develop this combination therapy as a novel therapeutic strategy for PVR.

키워드

Retinal pigment epithelial cell, PVR, SAHA, Lactacystin