Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5-and calcium-dependent regulation of autophagy

• 来源期刊: 中国药理学报（英文版）
• 关键词: propofol autophagy ATG5 calcium InsP3 receptors ryanodlne receptors mouse embryonic fibroblasts
• 年，卷（期）: 2020,（3）
• 页码范围: 303-310
• 页数: 8页
• 语种: 英文

摘要

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 ceils,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.