| Autor: |
Zheng-hao Zhang, Zi-guan Zhang, Min-wei Chen, Ying Yang, Run-jing Li, Jia-jia Xu, Cui Yang, Yu-ying Li, Hong-wei Chen, Shi-xiao Liu, Yan-ling Li, Ping Luo, Yi-jiang Liu, Wen-bo Chen, Zhong-gui Shan, Zheng-rong Huang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Oxidative Medicine and Cellular Longevity. |
| ISSN: |
1942-0900 |
| DOI: |
10.1155/2022/1115749 |
| Popis: |
The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD+ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putative PARP-1 inhibitor, reduced the myocardial injury caused by GSDMD deficiency. Our results reveal a novel action modality of GSDMD in the regulation of cardiomyocyte death; inhibition of GSDMD activates PARylation, suggesting the multidirectional role of GSDMD in I/R and providing a new theory for clinical treatment. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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