The mechanism of sinusoidal endothelial cell apoptosis induced by hydrogen peroxide derived from hepatocytes in hypoxic liver

低氧肝中肝细胞源过氧化氢诱导肝窦内皮细胞凋亡的机制

• 批准号: 10671396
• 负责人: SAITO Reijiro
• 金额: $ 2.24万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671396/
• 关键词: liver ischemia; hydrogen peroxide; sinusoidal endothelial cell; apoptosis; xanthine oxidase; Bcl-2; mitochonodria; 虚血肝障害

Bcl-2 is now recognized as a potent inhibitor of apoptotic cell death. In this study, we investigated the mechanism of sinusoidal endothelial cell apoptosis induced by hydrogen and liver protection using Bcl-2. Here we report that hypoxia induces xanthine oxidase-dependent hydrogen peroxide production in hepatocytes, and that this diffuses into sinusoidal endothelial cells and induces selective sinusoidal endothelial cells apoptosis in the blood-perfused rat liver. On the other hand, we reported that Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane and that Bcl-2 is expressed in normal rat liver, and locatedpredominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.

Bcl-2现在被认为是一种有效的凋亡细胞死亡抑制剂。在本研究中，我们探讨了氢诱导窦状内皮细胞凋亡的机制和Bcl-2的肝保护作用。在这里，我们报道了缺氧诱导肝细胞中黄嘌呤氧化酶依赖性过氧化氢的产生，并且这种过氧化氢扩散到血灌注大鼠肝脏的窦内皮细胞并诱导选择性窦内皮细胞凋亡。另一方面，我们报道Bcl-2位于线粒体、内质网和核膜中，并且Bcl-2在正常大鼠肝脏中表达，并且主要位于线粒体的内膜和嵴而不是外膜。

项目成果

S.Motoyama,R.Saito et al: "Bcl-2 is located predominantly in the inner membrare and Crista of mitochondria" Biochem.Biophys.Res.Commun.249. 628-636 (1998)

S.Motoyama、R.Saito 等人：“Bcl-2 主要位于线粒体的内膜和嵴”Biochem.Biophys.Res.Commun.249。

Motoyama S.et al.: "Hydrogen peroxide derived from hepatocytes induces sinuscidul emdotherial cell apoptosis in blood-perfused hypoxic rat liver"Gastrogenterology. 114. 153-163 (1998)

Motoyama S.等人：“来自肝细胞的过氧化氢诱导血液灌注缺氧大鼠肝脏中的窦内膜细胞凋亡”胃肠病学。

Motoyama,S et al.: "Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver"Biochemical Biophysic Research Communication. 249. 628-636 (1998)

Motoyama,S 等人：“Bcl-2 主要位于大鼠肝脏线粒体的内膜和嵴”《生化生物物理学研究通讯》。

S.Motoyama,R.Saito et al.: "Hydrogen peroxide derived from hepatolytes induces sinasoidal exlothelial cell apotoss" Gastroenterology. 114. 153-163 (1998)

S.Motoyama，R.Saito 等人：“来自肝细胞的过氧化氢诱导窦外皮细胞凋亡”胃肠病学。

Motoyama,S et al.: "Hydrogen peroxide derived from hepatocytes induces sinusoidal endotherial cell apoptosis in blood-perfused hypoxic rat liver"Gastroenterology. 114. 153-163 (1998)

Motoyama，S 等人：“来自肝细胞的过氧化氢诱导血液灌注缺氧大鼠肝脏中的窦内皮细胞凋亡”胃肠病学。