| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Atg5^(-/-)MEF(RCB2711) |
