RRC ID 43386
著者 Numazawa S, Sakaguchi H, Aoki R, Taira T, Yoshida T.
タイトル Regulation of the susceptibility to oxidative stress by cysteine availability in pancreatic beta-cells.
ジャーナル Am J Physiol Cell Physiol
Abstract Pancreatic beta-cells are susceptible to oxidative stress, which is related closely to the islet dysfunction. In the present study, using the pancreatic cell lines HIT-T15 and RINm5F as known in vitro models of impaired beta-cell function as well as primary rat islet beta-cells, we observed a relationship between intracellular glutathione levels and oxidative stress-mediated cell dysfunction. Hydrogen peroxide and 4-hydroxy-2-nonenal caused cell death in HIT-T15 and RINm5F cells at lower concentrations compared with non-beta-cells, such as HepG2 and NRK-49F cells. The extent of the cytotoxicity caused by the model oxidants was inversely correlated well with intracellular glutathione levels in the cell lines used. Treatment of HIT-T15 and RINm5F cells with l-cysteine or l-cystine significantly augmented the glutathione contents, surpassing the effect of N-acetylcysteine, and abrogated 4-hydroxy-2-nonenal-mediated cytotoxicity almost completely. l-Cysteine increased intracellular glutathione levels in primary beta-cells as well. Supplementation of l-cysteine to the RINm5F cell culture inhibited 4-hydroxy-2-nonenal-mediated cytosolic translocation of PDX-1, a key transcription factor for beta-cell function. Intrinsic transport activities (V(max)/K(m)) of the l-cystine/l-glutamate exchanger in HIT-T15 and RINm5F cells were considerably lower than that in NRK-49F cells, although gene expressions of the exchanger were similar in these cells. Results obtained from the present study suggest that the restricted activity of the l-cystine/l-glutamate exchanger controls the levels of intracellular glutathione, thereby making beta-cells become susceptible to oxidative stress.
巻・号 295(2)
ページ C468-74
公開日 2008-8-1
DOI 10.1152/ajpcell.00203.2008
PII 00203.2008
PMID 18524943
MeSH Acetylcysteine / metabolism Acetylcysteine / pharmacokinetics Aldehydes / pharmacology Amino Acid Transport System y+ / genetics Amino Acid Transport System y+ / metabolism Amino Acid Transport System y+ / physiology Animals Animals, Newborn Biological Transport / physiology Buthionine Sulfoximine / pharmacology Cell Line Cell Line, Tumor Cell Nucleus / metabolism Cell Survival / drug effects Cells, Cultured Cysteine / metabolism* Cysteine / pharmacology Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / metabolism Gene Expression Glutathione / antagonists & inhibitors Glutathione / metabolism Homeodomain Proteins / metabolism Humans Hydrogen Peroxide / pharmacology Insulin-Secreting Cells / cytology Insulin-Secreting Cells / drug effects Insulin-Secreting Cells / metabolism* Kinetics Oxidative Stress / physiology* Protein Transport / drug effects Rats Rats, Wistar Trans-Activators / metabolism
IF 3.485
引用数 15
WOS 分野 PHYSIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞