The Mechanism of Cell Death during Hypoxia

缺氧时细胞死亡的机制

• 批准号: 18590628
• 负责人: IWASE Hirotaro
• 金额: $ 2.34万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590628/
• 关键词: hypoxia; lipid peroxidation; active oxygen; forensic medicine; cell death

Many reseaithers indicate that lipid peroxidation and other oxidants occur in dell damage during ischemia-reperfusion. However it is still not clear that whether oxidants occur during ischemia or reperfusion phase. In this study, mouse emdryonic fibroblasts (MEFs) were used for experiment, to see how and when the oxidants occur during ischemia (reperfusion, or hypoxia and reoxygenation.). Some antioxidants or inhibitors of electron transfer system were treated for the cells to see the mechanism of lipid peroxidation. We used fluorescent dyes to detect the lipid peroxidation and dell damage. As a result, cell death occurs from ischemia pahase, and 63.9% cells were dead after reperfusion. Cell death was inhibited by KCN. Cell death during ischemia was inhibited by antimycinAor myxothiazol, and that during reperfusion was not inhibited by them. Lipid peroxidation was detected during ischemia and not during reperfusion, and it was inhibited by KCN and was not by antimacin A, myxotiazol or rotenone. From these results it was indicated that lipid peroxidation did not cccur during reperfusion but did during ischemia, and KCN could inhibit cell death and lipid peroxidation during ischemia.

许多研究表明，缺血再灌注时，细胞发生脂质过氧化和氧化损伤。然而，氧化剂是否发生在缺血或再灌注阶段仍不清楚。本研究以小鼠胚胎成纤维细胞（MEFs）为实验材料，观察了氧化剂在缺血（再灌注或缺氧复氧）过程中的发生方式和时间。用抗氧化剂或电子传递系统抑制剂处理细胞，观察脂质过氧化作用的机制。采用荧光染料法检测脂质过氧化和细胞损伤。结果表明，缺血期细胞死亡，再灌注后63.9%的细胞死亡。KCN可抑制细胞死亡。抗霉素A和粘噻唑可抑制缺血时的细胞死亡，但对再灌注时的细胞死亡无抑制作用。脂质过氧化反应在缺血期间检测到，而不是在再灌注期间，它被KCN抑制，而不是由抗霉素A，myxotiazol或鱼藤酮。结果表明，再灌注时不发生脂质过氧化反应，而缺血时发生脂质过氧化反应，KCN能抑制缺血时细胞死亡和脂质过氧化反应。

项目成果

Oxidant stress during simulated ischemia primes cardiomyocytes for cell death during reperfusion

• DOI: 10.1074/jbc.m701917200
• 发表时间: 2007-06-29
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Robin, Emmanuel;Guzy, Robert D.;Schumacker, Paul T.
• 通讯作者: Schumacker, Paul T.

Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes

• DOI: 10.1016/j.freeradbiomed.2007.05.017
• 发表时间: 2007-08-15
• 期刊: FREE RADICAL BIOLOGY AND MEDICINE
• 影响因子: 7.4
• 作者: Iwase, Hirotaro;Robin, Emmanuel;Schumacker, Paul T.
• 通讯作者: Schumacker, Paul T.