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Variable responses of small and large human hepatocytes to hypoxia and hypoxia/reoxygenation (H–R)
Author(s) -
Bhogal Ricky H.,
Weston Christopher J.,
Curbishley Stuart M.,
Bhatt Anand N.,
Adams David H.,
Afford Simon C.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.02.030
Subject(s) - hypoxia (environmental) , hepatocyte , apoptosis , microbiology and biotechnology , flow cytometry , intracellular , reactive oxygen species , mitochondrion , biology , programmed cell death , mitochondrial ros , in vitro , chemistry , oxygen , biochemistry , organic chemistry
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.