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A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death.
MedLine Citation:
PMID:  21479420     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Hidetaka Shibata; Tatsuki Ichikawa; Kazuhiko Nakao; Hisamitsu Miyaaki; Shigeyuki Takeshita; Motohisa Akiyama; Masumi Fujimoto; Satoshi Miuma; Shougo Kanda; Hironori Yamasaki; Katsumi Eguchi
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular medicine reports     Volume:  1     ISSN:  1791-2997     ISO Abbreviation:  Mol Med Report     Publication Date:    2008 May-Jun
Date Detail:
Created Date:  2011-04-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101475259     Medline TA:  Mol Med Report     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  379-85     Citation Subset:  -    
Affiliation:
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan.
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