Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac cells following ischemia and reperfusion

Parameswaran, Sreejit; Sharma, Rajendra K.

doi:10.1016/j.bbrc.2013.12.019

Cited by 8 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have reported increases in calpain-1/2 expression and activities in cardiomyocytes following ischemia/re-oxygenation [32] that contribute to cardiomyocyte apoptosis [9–11]. The up-regulation of calpain has also been observed in ischemic hearts [15,17, 33].…”

Section: Discussionmentioning

confidence: 99%

Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation

Zheng

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Both calpain activation and endoplasmic reticulum (ER) stress are implicated in ischemic heart injury. However, the role of calpain in ER stress remains largely elusive. This study investigated whether calpain activation causes ER stress, thereby mediating cardiomyocyte apoptosis in an in vitro model of hypoxia/re-oxygenation (H/R). In neonatal mouse cardiomyocytes and rat cardiomyocyte-like H9c2 cells, up-regulation of calpain-1 sufficiently induced ER stress, c-Jun N-terminal protein kinase1/2 (JNK1/2) activation and apoptosis. Inhibition of ER stress or JNK1/2 prevented apoptosis induced by calpain-1. In an in vitro model of H/R-induced injury in cardiomyocytes, H/R was induced by a 24-hour hypoxia followed by a 24-hour re-oxygenation. H/R activated calpain-1, induced ER stress and JNK1/2 activation, and triggered apoptosis. Inhibition of calpain and ER stress blocked JNK1/2 activation and prevented H/R-induced apoptosis. Furthermore, blockade of JNK1/2 signaling inhibited apoptosis following H/R. The role of calpain in ER stress was also demonstrated in an in vivo model of ischemia/reperfusion using transgenic mice over-expressing calpastatin. In summary, calpain-1 induces ER stress and JNK1/2 activation, thereby mediating apoptosis in cardiomyocytes. Accordingly, inhibition of calpain prevents ER stress, JNK1/2 activation and apoptosis in H/R-induced cardiomyocytes. Thus, ER stress/JNK1/2 activation may represent an important mechanism linking calpain-1 to ischemic injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation

Zheng

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

show abstract

“…These proteins act in a regulated and concerted manner for the proper functioning of heart muscle. Not much is known about the regulation and interaction among these proteins and associated molecules during cardiac injury caused by ischemia and reperfusion (I/R) [8] – [11] .…”

Section: Introductionmentioning

confidence: 99%

“…In normal myocardium, HMWCaMBP may protect its substrate from calpains. However during I/R, due to increased Ca 2+ influx, calpain activity often exceeds HMWCaMBP activity [8] , [16] . This leads to proteolysis of HMWCaMBP and other protein substrates, resulting in cellular damage.…”

Section: Introductionmentioning

confidence: 99%

“…The role of Calp and its homologue HMWCaMBP in I/R and their interactions are not completely elucidated [9] . In our previous report, this assay helped in determining cells which can survive I/R injury and most importantly the proteins responsible for the same [8] . Previous studies showed that HMWCaMBP and Calp interact with Calpn and regulates degradation of cellular proteins which results in the death of cardiac cells following I/R [8] – [10] , [12] – [16] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ischemia and Reperfusion Induce Differential Expression of Calpastatin and Its Homologue High Molecular Weight Calmodulin-Binding Protein in Murine Cardiomyocytes

Parameswaran

Sharma

2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

In the heart, calpastatin (Calp) and its homologue high molecular weight calmodulin-binding protein (HMWCaMBP) regulate calpains (Calpn) by inhibition. A rise in intracellular myocardial Ca2+ during cardiac ischemia activates Calpn thereby causing damage to myocardial proteins, which leads to myocyte death and consequently to loss of myocardial structure and function. The present study aims to elucidate expression of Calp and HMWCaMBP with respect to Calpn during induced ischemia and reperfusion in primary murine cardiomyocyte cultures. Ischemia and subsequently reperfusion was induced in ∼80% confluent cultures of neonatal murine cardiomyocytes (NMCC). Flow cytometric analysis (FACS) has been used for analyzing protein expression concurrently with viability. Confocal fluorescent microscopy was used to observe protein localization. We observed that ischemia induces increased expression of Calp, HMWCaMBP and Calpn. Calpn expressing NMCC on co-expressing Calp survived ischemic induction compared to NMCC co-expressing HMWCaMBP. Similarly, living cells expressed Calp in contrast to dead cells which expressed HMWCaMBP following reperfusion. A significant difference in the expression of Calp and its homologue HMWCaMBP was observed in localization studies during ischemia. The current study adds to the existing knowledge that HMWCaMBP could be a putative isoform of Calp. NMCC on co-expressing Calp and Calpn-1 survived ischemic and reperfusion inductions compared to NMCC co-expressing HMWCaMBP and Calpn-1. A significant difference in expression of Calp and HMWCaMBP was observed in localization studies during ischemia.

show abstract

“…Lugli et al have described calpain‐dependent activation of Dicer in neurons . Calpain is known as calcium‐dependent protease, whose inhibition has proved successful in treating ischemia‐reperfusion cardiac injury . Nevertheless, contribution of Dicer and miRNAs to activity of calpains in the heart is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Stress response factors as hub‐regulators of microRNA biogenesis: implication to the diseased heart

Gurianova

Stroy

Ciccocioppo

et al. 2015

Cell Biochemistry & Function

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are important regulators of heart function and then an intriguing therapeutic target for plenty of diseases. The problem raised is that many data in this area are contradictory, thus limiting the use of miRNA-based therapy. The goal of this review is to describe the hub-mechanisms regulating the biogenesis and function of miRNAs, which could help in clarifying some contradictions in the miRNA world. With this scope, we analyse an array of factors, including several known agents of stress response, mediators of epigenetic changes, regulators of alternative splicing, RNA editing, protein synthesis and folding and proteolytic systems. All these factors are important in cardiovascular function and most of them regulate miRNA biogenesis, but their influence on miRNAs was shown for non-cardiac cells or some specific cardiac pathologies. Finally, we consider that studying the stress response factors, which are upstream regulators of miRNA biogenesis, in the diseased heart could help in (1) explaining some contradictions concerning miRNAs in heart pathology, (2) making the role of miRNAs in pathogenesis of cardiovascular disease more clear, and therefore, (3) getting powerful targets for its molecular therapy.

show abstract

Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac cells following ischemia and reperfusion

Cited by 8 publications

References 37 publications

Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation

Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation

Ischemia and Reperfusion Induce Differential Expression of Calpastatin and Its Homologue High Molecular Weight Calmodulin-Binding Protein in Murine Cardiomyocytes

Stress response factors as hub‐regulators of microRNA biogenesis: implication to the diseased heart

Contact Info

Product

Resources

About