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A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death

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Title: A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death
Authors: Shibata, Hidetaka / Ichikawa, Tatsuki / Nakao, Kazuhiko / Miyaaki, Hisamitsu / Takeshita, Shigeyuki / Akiyama, Motohisa / Fujimoto, Masumi / Miuma, Satoshi / Kanda, Shougo / Yamasaki, Hironori / Eguchi, Katsumi
Issue Date: May-2008
Publisher: Spandidos Publications
Citation: Molecular Medicine Reports, 1(3), pp.379-385; 2008
Abstract: Oxidative stress is known to play a key role in the progression of liver disease, including non-alcoholic steatohepatitis (NASH), which is often accompanied by hyperglycemia. This study examined the influence of high glucose on oxidative stress-induced hepatic cell death. Hc cells, a normal human hepatocyte-derived cell line, were cultured in normal-to-high glucose (5.5-22 mM)-containing medium with varying concentrations (0.01-1 mM) of hydrogen peroxide. In certain experiments, cyclosporine A (CyA), which inhibits the mitochondrial permeability transition (MPT) pore, or Z-VAD-FMK (z-VAD), a pan-caspase inhibitor, were added to the medium. Cell viability was evaluated using a colorimetric assay. The mode of cell death was determined by nuclear staining methods using Hoechst 33258 and Sytox green. Neither high glucose (22 mM) nor 0.05-0.5 mM of hydrogen peroxide alone killed Hc cells. However, a combination of the two induced cell death, causing the nuclei of Hc cells to become expanded rather than condensed, and the nuclear membrane to become weak. CyA, but not z-VAD, blocked cell death. These results suggest that a high glucose condition may cause human hepatocytes to undergo hydrogen peroxide-induced necrotic cell death.
Keywords: high glucose / reactive oxygen species / hepatocyte cell death / necrosis / cyclosporine A
URI: http://hdl.handle.net/10069/22341
ISSN: 17912997
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22341

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