Inhibition of GSDMD Activates Poly(ADP-ribosyl)ation and Promotes Myocardial Ischemia-Reperfusion Injury.
Inhibition of GSDMD Activates Poly(ADP-ribosyl)ation and Promotes Myocardial Ischemia-Reperfusion Injury.
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抑制 GSDMD 激活聚（ADP-核糖基）化并促进心肌缺血再灌注损伤
DOI：
10.1155/2022/1115749
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发表时间：
2022
影响因子：
--
通讯作者：
Huang, Zheng-rong
中科院分区：
文献类型：
--
作者：
Zhang, Zheng-hao;Zhang, Zi-guan;Chen, Min-wei;Yang, Ying;Li, Run-jing;Xu, Jia-jia;Yang, Cui;Li, Yu-ying;Chen, Hong-wei;Liu, Shi-xiao;Li, Yan-ling;Luo, Ping;Liu, Yi-jiang;Chen, Wen-bo;Shan, Zhong-gui;Huang, Zheng-rong
精确控制心肌细胞活性对于对抗心肌缺血再灌注损伤(I/R)是必要的，在I/R中，细胞凋亡和下垂可能参与了这一过程。最近的研究表明，GSDMD作为一种执行蛋白参与了下睑下垂的I/R过程。然而，它对其他形式的细胞死亡的影响尚不清楚。我们发现GSDMD和GSDMD-N在小鼠的I/R心肌中显著上调。在I/R急性期，GSDMD基因敲除可增强心肌对再灌注损伤的抵抗作用，而在慢性期，GSDMD基因敲除可加重再灌注损伤。从机制上讲，GSDMD基因缺失导致心肌细胞PAR化激活，NAD+和ATP消耗，导致心肌细胞凋亡。PJ34可能是一种PARP-1抑制剂，可减轻GSDMD缺乏引起的心肌损伤。我们的结果揭示了GSDMD在调节心肌细胞死亡中的一种新的作用方式；抑制GSDMD激活PAR化，提示GSDMD在I/R中的多方向作用，并为临床治疗提供新的理论。
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.
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影响因子：
3.8
作者：
Prasad R;Horton JK;Dai DP;Wilson SH
通讯作者：
Wilson SH
DOI：
10.1136/heartjnl-2015-307855
发表时间：
2016-03
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Bulluck H;Yellon DM;Hausenloy DJ
通讯作者：
Hausenloy DJ
影响因子：
16.6
作者：
Langelier, Marie-France;Zandarashvili, Levani;Pascal, John M.
通讯作者：
Pascal, John M.
影响因子：
9.5
作者：
Liu, Yi;Lian, Kun;Tao, Ling
通讯作者：
Tao, Ling
NF-κB-Gasdermin D（GSDMD）轴偶联氧化应激，NACHT，LRR和PYD结构域含有含量的蛋白3（NLRP3）炎症体炎症体介导的心肌细胞性心肌细胞凋亡后，心肌梗死后。
DOI：
10.12659/msm.908529
发表时间：
2018-08-30
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Lei Q;Yi T;Chen C
通讯作者：
Chen C