論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | NRK49F(RCB0112) Hep G2 |