論文 - 詳細
| RRC ID | 71607 |
|---|---|
| 著者 | Ishii M, Hagiwara T, Mori Y, Shimizu S. |
| タイトル | Involvement of TRPM2 and L-type Ca²⁺ channels in Ca²⁺ entry and cell death induced by hydrogen peroxide in rat β-cell line RIN-5F. |
| ジャーナル | J Toxicol Sci |
| Abstract |
Ca²⁺ overload is one of the mechanisms for H₂O₂-induced cell death in rat pancreatic β-cell line RIN-5F cells. RIN-5F cells express TRPM2, which is a Ca²⁺-permeable channel activated by H₂O₂, and voltage-dependent L-type Ca²⁺ channels, both of which induce Ca²⁺ entry by H₂O₂. This study examined the contribution of these channels to H₂O₂-induced Ca²⁺ entry and cell death in RIN-5F cells. Cytosolic Ca²⁺ concentration was measured using fura-2 as a Ca²⁺ indicator. Cell death was estimated by trypan blue exclusion. Pre-treatment with poly(ADP-ribose) polymerase (PARP) inhibitors, which inhibit TRPM2 activation, strongly reduced Ca²⁺ entry by H₂O₂. The PARP inhibitors used had no effect on the Ca²⁺ elevation by voltage-dependent L-type Ca²⁺ channels. On the other hand, pre-treatment with L-type Ca²⁺ channel blockers, which did not affect TRPM2 activation, partly reduced H₂O₂-induced Ca²⁺ entry. Treatment with PARP inhibitors but not L-type Ca²⁺ channel blockers, around the early phase in H₂O₂-induced Ca²⁺ elevation, also reduced the late phase. Moreover, H₂O₂-induced RIN-5F cell death was strongly attenuated by PARP inhibitors, in compared to L-type Ca²⁺ channel blockers. Our results suggest that TRPM2 channels rather than L-type Ca²⁺ channels primarily contribute to H₂O₂-induced Ca²⁺ entry and cell death. |
| 巻・号 | 39(2) |
| ページ | 199-209 |
| 公開日 | 2014-4-1 |
| DOI | 10.2131/jts.39.199 |
| PII | DN/JST.JSTAGE/jts/39.199 |
| PMID | 24646700 |
| MeSH | Animals Calcium / metabolism* Calcium Channel Blockers / pharmacology Calcium Channels, L-Type / drug effects Calcium Channels, L-Type / physiology* Cell Death / drug effects Cell Death / genetics Cell Line, Tumor Enzyme Inhibitors / pharmacology HEK293 Cells Humans Hydrogen Peroxide / adverse effects* Insulin-Secreting Cells / metabolism* Insulin-Secreting Cells / pathology* Insulinoma / metabolism* Insulinoma / pathology Poly(ADP-ribose) Polymerase Inhibitors Rats TRPM Cation Channels / metabolism TRPM Cation Channels / physiology* |
| IF | 2.831 |
| 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 | 293(RCB1637) |