Variable responses of small and large human hepatocytes to hypoxia and hypoxia/reoxygenation (H-R)

被引：13

作者：

Bhogal, Ricky H. ^{[1
]}

Weston, Christopher J. ^{[1
]}

Curbishley, Stuart M. ^{[1
]}

Bhatt, Anand N. ^{[1
]}

Adams, David H. ^{[1
]}

Afford, Simon C. ^{[1
]}

机构：

[1] Univ Birmingham, Sch Med, Inst Biomed Res, Ctr Liver Res,Sch Infect & Immun, Birmingham B15 2TT, W Midlands, England

来源：

FEBS LETTERS | 2011年 / 585卷 / 06期

基金：

英国惠康基金;

关键词：

Human hepatocytes; Reactive oxygen species; Apoptosis; Necrosis; Hypoxia; Liver injury; RAT; GLUTATHIONE; SEPARATION; CAPACITY;

D O I：

10.1016/j.febslet.2011.02.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Hypoxia and hypoxia-reoxygenation (H-R) regulate human hepatocyte cell death by mediating the accumulation of reactive oxygen species (ROS). Hepatocytes within the liver are organised into periportal (PP) and peri-venous (PV) subpopulations. PP and PV hepatocytes differ in size and function. We investigated whether PP and PV human hepatocytes exhibit differential susceptibility to hypoxic stress. Isolated hepatocytes were used in an in vitro model of hypoxia and H-R. ROS production and cell death were assessed using flow cytometry. PV, and not PP hepatocytes, accumulate intracellular ROS in a mitochondrial dependent manner during hypoxia and H-R. This increased ROS regulates hepatocyte apoptosis and necrosis via a mitochondrial pathway. These findings have implications on the understanding of liver injury and application of potential therapeutic strategies. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：935 / 941

页数：7

共 19 条

[1]

ZONAL REDOX CHANGES AS A CAUSE OF SELECTIVE PERIVENULAR HEPATOTOXICITY OF ALCOHOL [J].