Inhibition for the Low Flow Hypoxia-Induced Mitochondrial Dysfunction using Methylprednisolone and Bcl-2

使用甲基泼尼松龙和 Bcl-2 抑制低流量缺氧引起的线粒体功能障碍

• 批准号: 13671213
• 负责人: MOTOYAMA Satoru
• 金额: $ 0.32万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671213/
• 关键词: ischemic liver; apoptosis; hydrogen peroxide; glucocorticoid; mitochondria; Bcl-2; sinusoidal enddothelial cell; 虚血; メチルプレドニゾロン

1 Bcl-2 localizationBcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. We report that Bcl-2 is expressed in normal rat liver, and located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.2 The hypoxia-induced mitochondrial Bcl-2 declineThe apoptotic nonparenchymal cells, identified as SECs, were observed, predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchyma! ceils were stained. Mitochondrial Bcl-2 levels declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. Pretreatment with a specific xanthine oxidase inhibitor blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.3 The mechanism by which methyiprednisolone protects the ischermic liverPretreatment with 30 mg/kg, 10mg/kg or 3 mg/kg methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization, and enzyme leakage, though hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. The beneficial effect of methylprednisolone appears to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.

1 Bcl-2定位Bcl-2在某些细胞系中定位于线粒体、内质网和核膜，在正常人和大鼠肝脏中不表达。Bcl-2在正常大鼠肝脏中表达，主要位于内膜和嵴，而不是在外膜。2缺氧诱导的线粒体Bcl-2下降。将细胞染色。线粒体Bcl-2水平下降，在缺氧过程中显着，虽然没有细胞凋亡的形态学迹象是明显的。用特异性黄嘌呤氧化酶抑制剂预处理可阻断缺氧诱导的SEC细胞过氧化氢的产生，也可阻断缺氧诱导的SEC细胞凋亡和线粒体Bcl-2的下降。3甲基强的松龙保护缺血肝脏的机制30 mg/kg，10 mg/kg或3 mg/kg甲基强的松龙预处理可抑制缺氧诱导的SEC细胞线粒体膜去极化和酶渗漏，但窦状隙内皮细胞中的过氧化氢水平和凋亡不受影响。甲基强的松龙的有益作用似乎与其在缺氧条件下保护线粒体膜去极化的能力有关。

项目成果

Satoru Motoyama, Ed. EbadiM, Marwash J, Chopra PK: "Mitochondrial Ubiquinone (Coenzyme Q10): Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Prominent Press. (2002)

本山悟，编辑。

Satoru Motoyama, et al.: "Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver"J Surg Res. (in press).

Satoru Motoyama 等人：“Bcl-2 的过氧化氢依赖性下降诱导缺氧肝脏细胞凋亡”J Surg Res。

Satoru Motoyama, et al.: "Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver"J.Surg.Res.. (in press).

Satoru Motoyama 等人：“Bcl-2 的过氧化氢依赖性下降诱导缺氧肝脏细胞凋亡”J.Surg.Res..（出版中）。

Satoru Motoyama, et al.: "Mitochondrial Ubiquinone (Coenzyme Q1O) : Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Prominent Press, Ed.Ebadi M, Marwash J, Chopra RK.. 550 (2002)

Satoru Motoyama 等人：“线粒体泛醌（辅酶 Q1O）：人类健康和疾病中的生化、功能、医学和治疗方面”Prominent Press，Ed.Ebadi M、Marwash J、Chopra RK.. 550（2002）

Motoyama S et al.: "Mitochondrial Ubiquinone (Co enzyme Q10) : Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Ebadi M, Marwash J, Chopra RK Ed Prominent Press. 998 (2001)

Motoyama S 等人：“线粒体泛醌（辅酶 Q10）：人类健康和疾病的生化、功能、医学和治疗方面”Ebadi M、Marwash J、Chopra RK Ed Prominent Press。