Cardiac ischemia/reperfusion stress reduces inner mitochondrial membrane protein (mitofilin) levels during early reperfusion

Tombo, Nathalie; Aliagan, Abdulhafiz Imam; Feng, Yan; Singh, Harpreet; Bopassa, Jean C.

doi:10.1016/j.freeradbiomed.2020.06.039

Cited by 25 publications

(20 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We further reported that hypoxia/reoxygenation and global ischemia/reperfusion increased calpain-1 in the mitochondria of cultured cardiomyocytes and isolated whole hearts, respectively [42]. Similarly, other studies have demonstrated an increase in calpain activity in the mitochondria of ischemic heart [68,69]. These findings have implicated mito-calpain in cardiac pathology.…”

Section: Regulation Of Calpain Systemsupporting

confidence: 71%

Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease

Zhang

Wang

Peng

2021

Cells

View full text Add to dashboard Cite

Calpains belong to the family of calcium-dependent cysteine proteases expressed ubiquitously in mammals and many other organisms. Activation of calpain is observed in diseased hearts and is implicated in cardiac cell death, hypertrophy, fibrosis, and inflammation. However, the underlying mechanisms remain incompletely understood. Recent studies have revealed that calpains target and impair mitochondria in cardiac disease. The objective of this review is to discuss the role of calpains in mediating mitochondrial damage and the underlying mechanisms, and to evaluate whether targeted inhibition of mitochondrial calpain is a potential strategy in treating cardiac disease. We expect to describe the wealth of new evidence surrounding calpain-mediated mitochondrial damage to facilitate future mechanistic studies and therapy development for cardiac disease.

show abstract

Section: Regulation Of Calpain Systemsupporting

confidence: 71%

Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease

Zhang

Wang

Peng

2021

Cells

View full text Add to dashboard Cite

show abstract

“…Cardiomyocytes from adult 4-6 months old (minimum 300 g) rats were isolated following the procedures described in Ref. (58). Briefly, animals were injected intraperitoneally with heparin (200 IU/kg), and 20 min later, they were anesthetized with ketamine (80 mg•kg −1 i.p.)…”

Section: Isolation Of Adult Cardiomyocytesmentioning

confidence: 99%

Chronic GPER1 Activation Protects Against Oxidative Stress-Induced Cardiomyoblast Death via Preservation of Mitochondrial Integrity and Deactivation of Mammalian Sterile-20-Like Kinase/Yes-Associated Protein Pathway

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction: Estrogen (17β-estradiol, E2) is well-known to induce cardioprotective effects against ischemia/reperfusion (I/R) injury. We recently reported that acute application of E2 at the onset of reperfusion in vivo induces cardioprotective effects against I/R injury via activation of its non-steroidal receptor, G protein-coupled estrogen receptor 1 (GPER1). Here, we investigated the impact and mechanism underlying chronic GPER1 activation in cultured H9c2 rat cardiomyoblasts. Methods: H9c2 rat cardiomyoblasts were cultured and pretreated with the cytotoxic agent H 2 O 2 for 24 h and incubated in the presence of vehicle (control), GPER1 agonists E2 and G1, or GPER1 agonists supplemented with G15 (GPER1 antagonist) for 48 or 96 h. After treatment, cells were collected to measure the rate of cell death and viability using flow cytometry and Calcein AM assay or MTT assay, respectively. The resistance to opening of the mitochondrial permeability transition pore (mPTP), the mitochondrial membrane potential, and ATP production was assessed using fluorescence microscopy, and the mitochondrial structural integrity was observed with electron microscopy. The levels of the phosphorylation of mammalian sterile-20-like kinase (MST1) and yes-associated protein (YAP) were assessed by Western blot analysis in whole-cell lysate, while the expression levels of mitochondrial biogenesis genes, YAP target genes, and proapoptotic genes were measured by qRT-PCR. Results: We found that after H 2 O 2 treatment, chronic E2/G1 treatment decreased cell death effect was associated with the prevention of the S phase of the cell cycle arrest compared to control. In the mitochondria, chronic E2/G1 activation treatment preserved the cristae morphology, and increased resistance to opening of mPTP, but Imam Aliagan et al. Chronic GPER1 Actions and Cell Death with little change to mitochondrial fusion/fission. Additionally, chronic E2/G1 treatment predominantly reduced phosphorylation of MST1 and YAP, as well as increased MST1 and YAP protein levels. E2 treatment also upregulated the expression levels of TGFβ and PGC-1α mRNAs and downregulated PUMA and Bim mRNAs. Except for ATP production, all the E2 or G1 effects were prevented by the cotreatment with the GPER1 antagonist, G15. Conclusion: Together, these results indicate that chronic GPER1 activation with its agonists E2 or G1 treatment protects H9c2 cardiomyoblasts against oxidative stressinduced cell death and increases cell viability by preserving mitochondrial structure and function as well as delaying the opening of mPTP. These chronic GPER1 effects are associated with the deactivation of the non-canonical MST1/YAP mechanism that leads to genetic upregulation of cell growth genes (CTGF, CYR61, PGC-1α, and ANKRD1), and downregulation of proapoptotic genes (PUMA and Bim).

show abstract

“…Mitochondrial cristae are the main sites of ATP production and maintaining its normal structure is very crucial for mitochondrial function [ 21 ]. Abnormal mitochondrial cristae structure played a significant role in the progressions of several diseases [ 22 , 23 ]. In our previous study, we found that extracellular acidosis disrupted normal mitochondrial structure, including cristae, which suggested mitochondrial structure impairment might involve extracellular acidosis-induced mitochondrial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

TRAP1 inhibits MIC60 ubiquitination to mitigate the injury of cardiomyocytes and protect mitochondria in extracellular acidosis

Zhang

Luo

et al. 2021

Cell Death Discov.

View full text Add to dashboard Cite

Extracellular acidosis-induced mitochondrial damage of cardiomyocytes leads to cardiac dysfunction, but no detailed mechanism or efficient therapeutic target has been reported. Here we found that the protein levels of MIC60 were decreased in H9C2 cells and heart tissues in extracellular acidosis, which caused mitochondrial damage and cardiac dysfunction. Overexpression of MIC60 maintains H9C2 cells viability, increases ATP production and mitochondrial membrane potential, mitigates the disruptions of mitochondrial structure and cardiac injury. Mechanistically, extracellular acidosis excessively promoted MIC60 ubiquitin-dependent degradation. TRAP1 mitigated acidosis-induced mitochondrial impairments and cardiac injury by directly interacting with MIC60 to decrease its ubiquitin-dependent degradation in extracellular acidosis.

show abstract

Cardiac ischemia/reperfusion stress reduces inner mitochondrial membrane protein (mitofilin) levels during early reperfusion

Cited by 25 publications

References 45 publications

Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease

Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease

Chronic GPER1 Activation Protects Against Oxidative Stress-Induced Cardiomyoblast Death via Preservation of Mitochondrial Integrity and Deactivation of Mammalian Sterile-20-Like Kinase/Yes-Associated Protein Pathway

TRAP1 inhibits MIC60 ubiquitination to mitigate the injury of cardiomyocytes and protect mitochondria in extracellular acidosis

Contact Info

Product

Resources

About