Calpain: the Regulatory Point of Myocardial Ischemia-reperfusion Injury

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2023 Jul 17

PMID 37456811

Authors

Guo-Yang Liu

Wan-Li Xie

Yan-Ting Wang

Lu Chen

Zhen-Zhen Xu

Yong Lv

Qing-Ping Wu

Affiliations

Soon will be listed here.

Abstract

Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.

Citing Articles

Mechanisms of postischemic cardiac death and protection following myocardial injury.

Mastoor Y, Murphy E, Roman B J Clin Invest. 2025; 135(1).

PMID: 39744953 PMC: 11684816. DOI: 10.1172/JCI184134.

Efficacy and safety of levosimendan in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: The LEVOCEST trial.

Bosa Ojeda F, Mendez Vargas C, Lacalzada Almeida J, Izquierdo Gomez M, Jimenez Sosa A, Rodriguez Jimenez C Catheter Cardiovasc Interv. 2024; 104(7):1414-1422.

PMID: 39425551 PMC: 11667407. DOI: 10.1002/ccd.31267.

References

Martinez J, Zhang Z, Svetlov S, Hayes R, Wang K, Larner S . Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells. Apoptosis. 2010; 15(12):1480-93. DOI: 10.1007/s10495-010-0526-4. View

Inserte J, Hernando V, Garcia-Dorado D . Contribution of calpains to myocardial ischaemia/reperfusion injury. Cardiovasc Res. 2012; 96(1):23-31. DOI: 10.1093/cvr/cvs232. View

Wang K, Posmantur R, Nadimpalli R, Nath R, Mohan P, Nixon R . Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis. Arch Biochem Biophys. 1998; 356(2):187-96. DOI: 10.1006/abbi.1998.0748. View

Cha S, Cho C, Kim S, Cho J, Baek W, Suh M . Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells. Cancer Lett. 2002; 182(1):83-92. DOI: 10.1016/s0304-3835(02)00075-7. View

Sudhakar J, Lu H, Chiang H, Suen C, Hwang M, Wu S . Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas. Nat Commun. 2020; 11(1):4286. PMC: 7453023. DOI: 10.1038/s41467-020-18102-7. View

Riedl S, Shi Y . Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 2004; 5(11):897-907. DOI: 10.1038/nrm1496. View

Geronimo-Olvera C, Montiel T, Rincon-Heredia R, Castro-Obregon S, Massieu L . Autophagy fails to prevent glucose deprivation/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons. Cell Death Dis. 2017; 8(6):e2911. PMC: 5520945. DOI: 10.1038/cddis.2017.299. View

Chen Q, Paillard M, Gomez L, Ross T, Hu Y, Xu A . Activation of mitochondrial μ-calpain increases AIF cleavage in cardiac mitochondria during ischemia-reperfusion. Biochem Biophys Res Commun. 2011; 415(4):533-8. PMC: 3244491. DOI: 10.1016/j.bbrc.2011.10.037. View

Bonora M, Giorgi C, Pinton P . Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 2021; 23(4):266-285. DOI: 10.1038/s41580-021-00433-y. View

10.

Yue R, Lu S, Luo Y, Wang T, Liang H, Zeng J . Calpain silencing alleviates myocardial ischemia-reperfusion injury through the NLRP3/ASC/Caspase-1 axis in mice. Life Sci. 2019; 233:116631. DOI: 10.1016/j.lfs.2019.116631. View

11.

Levine B, Kroemer G . Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 2019; 176(1-2):11-42. PMC: 6347410. DOI: 10.1016/j.cell.2018.09.048. View

12.

Humphries F, Shmuel-Galia L, Ketelut-Carneiro N, Li S, Wang B, Nemmara V . Succination inactivates gasdermin D and blocks pyroptosis. Science. 2020; 369(6511):1633-1637. PMC: 8744141. DOI: 10.1126/science.abb9818. View

13.

Karamanlidis G, Lee C, Garcia-Menendez L, Kolwicz Jr S, Suthammarak W, Gong G . Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab. 2013; 18(2):239-50. PMC: 3779647. DOI: 10.1016/j.cmet.2013.07.002. View

14.

Shi H, Gao Y, Dong Z, Yang J, Gao R, Li X . GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury. Circ Res. 2021; 129(3):383-396. PMC: 8291144. DOI: 10.1161/CIRCRESAHA.120.318629. View

15.

Fink S, Cookson B . Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005; 73(4):1907-16. PMC: 1087413. DOI: 10.1128/IAI.73.4.1907-1916.2005. View

16.

Lee P, Sata M, Lefer D, Factor S, Walsh K, Kitsis R . Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo. Am J Physiol Heart Circ Physiol. 2002; 284(2):H456-63. DOI: 10.1152/ajpheart.00777.2002. View

17.

Dargelos E, Brule C, Stuelsatz P, Mouly V, Veschambre P, Cottin P . Up-regulation of calcium-dependent proteolysis in human myoblasts under acute oxidative stress. Exp Cell Res. 2009; 316(1):115-25. DOI: 10.1016/j.yexcr.2009.07.025. View

18.

Clapham D . Calcium signaling. Cell. 2007; 131(6):1047-58. DOI: 10.1016/j.cell.2007.11.028. View

19.

Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T . Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res. 2007; 100(6):914-22. DOI: 10.1161/01.RES.0000261924.76669.36. View

20.

Yamashima T . Can 'calpain-cathepsin hypothesis' explain Alzheimer neuronal death?. Ageing Res Rev. 2016; 32:169-179. DOI: 10.1016/j.arr.2016.05.008. View