title: A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death.
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.
authors.affiliation: The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shibata
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Miyaaki
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Takeshita
authors.forename: Motohisa
authors.initials: M
authors.lastname: Akiyama
authors.forename: Masumi
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miuma
authors.forename: Shougo
authors.initials: S
authors.lastname: Kanda
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi