論文 - 詳細
| RRC ID | 38564 |
|---|---|
| 著者 | Araki M, Maeda M, Motojima K. |
| タイトル | Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Statins are the most common type of medicine used to treat hypercholesterolemia; however, they are associated with a low incidence of myotoxicity such as myopathy and rhabdomyolysis. The mechanisms for the adverse effects remain to be fully elucidated for safer chronic use and drug development. The results of our earlier work suggested that hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma A204 cells. In this study, we first confirmed the statin-induced autophagy by assessing other criteria, including induced expression of the autophagy-related genes, enhanced protein degradation of autophagy marker protein p62 and electron microscopic observation of induced formation of autophagosome. We next demonstrated that the extent of inhibition of HMG-CoA reductase in the cell is parallel with the ability of a statin to induce autophagy. Thus, the primary activity of statins causes autophagy in A204 cells. Considering the mechanism for the induction, we showed that statins induce autophagy by depleting cellular levels of geranylgeranyl diphosphate (GGPP) mostly through an unknown pathway that does not involve two major small G proteins, Rheb and Ras. Finally, we demonstrated that the ability of statins to induce autophagy parallels their toxicity to A204 cells and that both can be suppressed by GGPP. |
| 巻・号 | 674(2-3) |
| ページ | 95-103 |
| 公開日 | 2012-1-15 |
| DOI | 10.1016/j.ejphar.2011.10.044 |
| PII | S0014-2999(11)01430-0 |
| PMID | 22094060 |
| MeSH | Autophagy / drug effects* Cell Line, Tumor Humans Hydrophobic and Hydrophilic Interactions* Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry* Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Microtubule-Associated Proteins / metabolism Monomeric GTP-Binding Proteins / antagonists & inhibitors Neuropeptides / antagonists & inhibitors Polyisoprenyl Phosphates / metabolism* Ras Homolog Enriched in Brain Protein Rhabdomyosarcoma / pathology* |
| IF | 3.263 |
| 引用数 | 34 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |