3,4-benzopyrene aggravates myocardial ischemia–reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation

Huang, Kaiyu; Liu, Shuai; Yu, Yong-Wei; Wu, Bo-Sen; Lin, Zhi-hui; Zhu, Chen-xi; Song, Dong-Yan; Xue, Yan; Ji, Kangting

doi:10.1016/j.ecoenv.2023.114701

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…The Dox treatment significantly blocked the autophagic flux in the heart, and the impaired autophagosome clearance was closely related to cell death 20 . P62 is capable of transporting damaged organelles to the autophagosome, so accumulation of P62 indicates clearance of damage 21 . We investigated the role of autophagy in the Dox‐induced cardiotoxicity and the effects of DHA on autophagy.…”

Section: Resultsmentioning

confidence: 99%

“…20 P62 is capable of transporting damaged organelles to the autophagosome, so accumulation of P62 indicates clearance of damage. 21 We investigated the role of autophagy in the Dox-induced cardiotoxicity and the effects of DHA on autophagy. Using western blot analysis, we examined the levels of autophagy-related proteins ATG5, P62, and LC3B in vivo and found that Dox increased the protein expression levels of ATG5, P62, and LC3BII.…”

Section: Dha Promoted Autophagic Flux In Vivo and In Vitromentioning

confidence: 99%

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Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

Lin,

Xiang,

et al. 2024

The FASEB Journal

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Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox‐induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin‐induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real‐time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox‐induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox‐induced cardiotoxicity. In addition, DHA significantly alleviates Dox‐induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

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Section: Resultsmentioning

confidence: 99%

Section: Dha Promoted Autophagic Flux In Vivo and In Vitromentioning

confidence: 99%

Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

Lin,

Xiang,

et al. 2024

The FASEB Journal

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“…Previous studies suggested that the modes of cell death in cardiomyocytes during ischemia/reperfusion (I/R) primarily consist of apoptosis, necroptosis, and autophagy (Zhang et al, 2023). However, recent research has found that pyroptosis is also involved in regulating the severity of MIRI (Huang et al, 2023). Pyroptosis is a newly discovered form of cell necrosis in recent years, characterized as a pro‐inflammatory, programmed cell necrosis (Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…However, recent research has found that pyroptosis is also involved in regulating the severity of MIRI (Huang et al, 2023). Pyroptosis is a newly discovered form of cell necrosis in recent years, characterized as a proinflammatory, programmed cell necrosis .…”

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confidence: 99%

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Zhang,

Wu,

Liu

et al. 2023

Cell Biology International

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Alleviating myocardial ischemia‐reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIPL, and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia‐reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIPL expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIPL can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD‐N, IL‐1β, and IL‐18 proteins, promoting cell apoptosis. Our research indicates that cFLIPL may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIPL could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.

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The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery

Deng,

Liu,

et al. 2024

Biomedicine & Pharmacotherapy

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3,4-benzopyrene aggravates myocardial ischemia–reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation

Cited by 7 publications

References 46 publications

Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery

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3,4-benzopyrene aggravates myocardial ischemia–reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation

Cited by 7 publications

References 46 publications

Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

Dihydroartemisinin alleviates doxorubicin‐induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy

cFLIPL alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery

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cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis