Abstract
AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference46 articles.
1. Li, H., Zou, T., Meng, S., Peng, Y. Z. & Yang, J. F. p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting oxidative stress. Mol. Med. Rep. 17, 4665–4671 (2018).
2. Sukhotnik, I. et al. Effect of N-acetylserotonin on TLR-4 and MyD88 expression during intestinal ischemia-reperfusion in a rat model. Eur. J. Pediatr. Surg. 29, 188–195 (2019).
3. Zhang, P. et al. WITHDRAWN: Schisandrin B suppresses NLRP3 inflammasome activation to alleviate myocardial ischemia reperfusion injury via maintaining mitochondrial autophagy. Biochem. Biophys. Res. Commun. 494, 425 (2017).
4. Ma, H. J. et al. Chronic intermittent hypobaric hypoxia ameliorates ischemia/reperfusion-induced calcium overload in heart via Na/Ca2+ exchanger in developing rats. Cell Physiol. Biochem. 34, 313–324 (2014).
5. Wang, Y. et al. Large-conductance Ca(2+)-activated K(+) channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture at Shuigou (GV26) acupoint in rats. Neural Regen. Res. 11, 957–962 (2016).
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