上睑下垂
自噬
化学
心脏毒性
芳香烃受体
药理学
再灌注损伤
细胞生物学
细胞凋亡
程序性细胞死亡
缺血
医学
生物化学
生物
毒性
内科学
转录因子
基因
有机化学
作者
Kaiyu Huang,Shuai Liu,Yong-Wei Yu,Bo-Sen Wu,Zhi-hui Lin,Chen-xi Zhu,Dong-Yan Song,Yan Xue,Kangting Ji
标识
DOI:10.1016/j.ecoenv.2023.114701
摘要
Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia–reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation–reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53–BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53–BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.
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