KR 31378, a Potent Antioxidant, Inhibits Apoptotic Death of A7r5 Cells

• 영문명: KR 31378, a Potent Antioxidant, Inhibits Apoptotic Death of A7r5 Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Ki Young Kim Byeong Gee Kim Sun-Ok Kim Sung-Eun Yoo Ki Whan Hong
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제5권 제5호, 381~388쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2001.01.01

영문 초록

This work describes the pharmacological inhibition by KR 31378 and its acetyl metabolite, KR 31612, of the apoptotic cell death induced by H₂O₂ in the A7r5 cells. Exposure of A7r5 cells to H₂O₂ (0.5 mM) induced a concentration-dependent cytotoxicity in association with oligonucleosomal DNA fragmentation. H₂O₂-induced cell death was potently suppressed by KR 31378, KR 31612, α-tocopherol or trolox. Additionally, the apoptotic death of A7r5 cells (DNA ladders on electrophoresis) was also strongly suppressed by KR 31378 and KR 31612, but to a less degree by α-tocopherol and trolox. As a mechanistic study, incubation with H₂O₂ markedly showed a decreased Bcl-2 level and, in contrast, increased Bax protein and cytochrome C release, which were significantly and concentration-dependently reversed by KR 31378 and KR 31612 as well as by α-tocopherol and trolox. KR 31378 and α-tocopherol significantly reduced lipid peroxidation in accordance with reduced intracellular ROS and peroxyl radical. These results suggest that KR 31378 has a therapeutic potential against the apoptotic injury via mediation of anti- oxidative stress.

키워드

KR 31378 α-Tocopherol Oxidative stress Apoptosis Reactive oxygen species Bcl-2 Bax Cytochrome C