論文 - 詳細
| RRC ID | 58121 |
|---|---|
| 著者 | Xu ZD, Wang Y, Liang G, Liu ZQ, Ma WH, Chu CT, Wei HF. |
| タイトル | Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5- and calcium-dependent regulation of autophagy. |
| ジャーナル | Acta Pharmacol Sin |
| Abstract |
Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of autophagy-related gene 5 (ATG5) in propofol-induced autophagy in mouse embryonic fibroblasts (MEF) in vitro. We showed that ATG5 was functionally related to propofol-induced cell survival and damage: propofol significantly enhanced cell survival and proliferation at a clinically relevant dose (10 µM), but caused cell death at an extremely high concentration (200 µM) in ATG5-/- MEF, but not in WT cells. The dual effects found in ATG5-/- MEF could be blocked by intracellular Ca2+ channel antagonists. We also found that propofol evoked a moderate (promote cell growth) and extremely high (cause apoptosis) cytosolic Ca2+ elevation at the concentrations of 10 µM and 200 µM, respectively, only in ATG5-/- MEF. In addition, ATG5-/- MEF themselves released more Ca2+ in cytosolic space and endoplasmic reticulum compared with WT cells, suggesting that autophagy deficiency made intracellular calcium signaling more vulnerable to external stimuli (propofol). Altogether, our results reveal that ATG5 plays a crucial role in propofol regulation of cell survival and proliferation by affecting intracellular Ca2+ homeostasis. |
| 巻・号 | 41(3) |
| ページ | 303-310 |
| 公開日 | 2020-3-1 |
| DOI | 10.1038/s41401-019-0303-z |
| PII | 10.1038/s41401-019-0303-z |
| PMID | 31645660 |
| PMC | PMC7471456 |
| MeSH | Anesthetics, Intravenous / pharmacology* Animals Autophagy / drug effects* Autophagy-Related Protein 5 / deficiency Autophagy-Related Protein 5 / metabolism* Calcium / metabolism* Cell Proliferation / drug effects Cell Survival / drug effects Cells, Cultured Dose-Response Relationship, Drug Fibroblasts / drug effects* Mice Mice, Knockout Propofol / pharmacology* Structure-Activity Relationship |
| IF | 5.064 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 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 | Atg5^(-/-)MEF(RCB2711) |