自噬
纤维化
心脏纤维化
脂质过氧化
GPX4
细胞生物学
化学
基因敲除
KEAP1型
氧化应激
癌症研究
生物
医学
细胞凋亡
生物化学
超氧化物歧化酶
病理
转录因子
基因
谷胱甘肽过氧化物酶
作者
Huaifang Hu,Lipeng Li,Huaxing Zhang,Yaling Zhang,Qingping Liu,Mei-Yu Chen,Jie Ning,Yaxian Pang,Wentao Hu,Yujie Niu,Rong Zhang
出处
期刊:Chemosphere
[Elsevier]
日期:2023-02-01
卷期号:315: 137749-137749
被引量:11
标识
DOI:10.1016/j.chemosphere.2023.137749
摘要
Epidemiological studies have demonstrated strong associations between exposure to ambient fine particulate matter (PM2.5) and cardiac disease. To investigate the potential mechanism of cardiac fibrosis induced by PM2.5, we established PM2.5 exposure models in vivo and in vitro, and then cardiac fibrosis was evaluated. The ferroptosis and ferritinophagy was detected to characterize the effects of PM2.5 exposure. The results indicated that PM2.5 exposure could induce cardiac fibrosis in mice. YY1 was induced by PM2.5 exposure and then increased NCOA4, a cargo receptor for ferritinophagy, which interacted with FHC and promoted the transport of ferritin to the autophagosome for degradation. The release of large amounts of free iron from ferritinophagy led to lipid peroxidation directly via the Fenton reaction, thereby triggering ferroptosis. Moreover, siNCOA4 could partly restore the FHC protein level in HL-1 cells and inhibit the occurrence of downstream ferroptosis. Functionally, NCOA4 knockdown inhibited ferroptosis and alleviated HL-1 cell death induced by PM2.5. Ferroptosis inhibitor (Ferrostatin-1) could reverse the promoting effect of ferritinophagy mediated ferroptosis on cardiac fibrosis induced by PM2.5 exposure in mice. Our study indicated that PM2.5 induced cardiac fibrosis through YY1 regulating ferritinophagy-dependent ferroptosis.
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