Sonic hedgehog signaling facilitates pyroptosis in mouse heart following ischemia/reperfusion via enhancing the formation of CARD10-BCL10-MALT1 complex.

Autor: Li MR; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Lu LQ; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Zhang YY; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Yao BF; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Tang C; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Dai SY; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China., Luo XJ; Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, China. Electronic address: xjluo22@csu.edu.cn., Peng J; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China. Electronic address: junpeng@csu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Dec 05; Vol. 984, pp. 177019. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1016/j.ejphar.2024.177019
Abstrakt: Pyroptosis has been found to contribute to myocardial ischemia/reperfusion (I/R) injury, but the exact mechanisms that initiate myocardial pyroptosis are not fully elucidated. Sonic hedgehog (SHH) signaling is activated in heart suffered I/R, and intervention of SHH signaling has been demonstrated to protect heart from I/R injury. Caspase recruitment domain-containing protein 10 (CARD10)-B cell lymphoma 10 (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex could transduce signals from the membrane and induce inflammatory pathways in non-hematopoietic cells, which could be a downstream effector of SHH signaling pathway. This study aims to explore the role of SHH signaling in I/R-induced myocardial pyroptosis and its relationship with the CBM complex. C57BL/6J mice were subjected to 45 min-ischemia followed by 24 h-reperfusion to establish a myocardial I/R model, and H9c2 cells underwent hypoxia/reoxygenation (H/R) to mimic myocardial I/R model in vitro. Firstly, SHH signaling was significantly activated in heart suffered I/R in an autocrine- or paracrine-dependent manner via its receptor PTCH1, and inhibition of SHH signaling decreased myocardial injury via reducing caspase-11-dependent pyroptosis, concomitant with attenuating CBM complex formation. Secondly, suppression of SHH signaling decreased protein kinase C α (PKCα) level, but inhibition of PKCα attenuated CBM complex formation without impacting the protein levels of SHH and PTCH1. Finally, disruption of the CBM complex prevented MALT1 from recruiting of TRAF6, which was believed to trigger the caspase-11-dependent pyroptosis. Based on these results, we conclude that inhibition of SHH signaling suppresses pyroptosis via attenuating PKCα-mediated CARD10-BCL10-MALT1 complex formation in mouse heart suffered I/R.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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