Methamphetamine mediates apoptosis of vascular smooth muscle cells via the chop-related endoplasmic reticulum stress pathway. (10th October 2021)

• Record Type: Journal Article
• Authors: Tan, Xiaohui; Cai, Dunpeng; Chen, Na; Du, Sihao; Qiao, Dongfang; Yue, Xia; Wang, Tao; Li, Jia; Xie, Weibing; Wang, Huijun
• Is Part Of: Toxicology letters. Volume 350(2021)
• Page Start: 98
• Page End: 110
• Publication Date: 2021-10-10
• Subjects: Methamphetamine -- Vascular smooth muscle cell -- Endoplasmic reticulum stress -- Chop -- Apoptosis; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.06.019
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: Methamphetamine (METH) is a highly addictive amphetamine-type drug that has caused persistent harm to society and human health in recent years. Most studies have shown that METH severely damages the central nervous system, and this drug has been found to be toxic to the cardiovascular system in recent years. Therefore, we hypothesized that METH may also damage vascular smooth muscle. We examined the expression of the apoptosis-related proteins Caspase 3 and PARP after METH treatment in vivo and in vitro and detected the expression of endoplasmic reticulum stress-related proteins. After treatment with the endoplasmic reticulum stress inhibitor 4-PBA, changes in the above indicators were examined. C/EBP homologous protein (Chop) expression was also detected, and the relationship between endoplasmic reticulum stress and apoptosis was further determined by siRNA silencing of Chop. The results indicated that METH can induce apoptosis of vascular smooth muscle cells (VSMCs) and upregulate the expression of Chop and endoplasmic reticulum stress-related proteins. Chop inhibits protein kinase B phosphorylation and further inhibits forkhead box class O3a (Foxo3a) dephosphorylation, resulting in increased p53 upregulated molecular of apoptosis (PUMA) transcription. Increased PUMA induces apoptosis through the mitochondrial pathway. These results indicate that Chop is involved in the METH-induced endoplasmic reticulum stress and apoptosis in VSMCs and may be a potential therapeutic target for METH-induced VSMC injury.