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

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Colleges, School and Institutes

Abstract

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 peri-portal (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.

Details

Original languageEnglish
Pages (from-to)935-941
Number of pages7
JournalFEBS Letters
Volume585
Issue number6
Publication statusPublished - 23 Mar 2011

Keywords

  • Human hepatocytes; Reactive oxygen species; Apoptosis; Necrosis; Hypoxia; Liver injury