ArticleArchives of toxicology2019
Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity.
Article in Archives of toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.Cardiovascular diabetology · 2026Article
- Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferationActa pharmaceutica Sinica. B · 2023Article
- Sustained over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice through aberrant autophagy.Acta pharmacologica Sinica · 2022Article
- Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria.Life (Basel, Switzerland) · 2022Article
- MicroRNA-495-3p diminishes doxorubicin-induced cardiotoxicity through activating AKT.Journal of cellular and molecular medicine · 2022Article
- Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease.Cells · 2021Review
- Loss of TRIM21 alleviates cardiotoxicity by suppressing ferroptosis induced by the chemotherapeutic agent doxorubicin.EBioMedicine · 2021Article
- Targeted inhibition of calpain in mitochondria alleviates oxidative stress-induced myocardial injury.Acta pharmacologica Sinica · 2021Article
- Sodium nitrate co-supplementation does not exacerbate low dose metronomic doxorubicin-induced cachexia in healthy mice.Scientific reports · 2020Article
- Endoplasmic reticulum stress-induced complex I defect: Central role of calcium overload.Archives of biochemistry and biophysics · 2020Article
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Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
Abstract
We recently reported that doxorubicin decreased the expression of calpain-1/2, while inhibition of calpain activity promoted doxorubicin-induced cardiac injury in mice. In this study, we investigated whether and how elevation of calpain-2 could affect doxorubicin-triggered cardiac injury. Transgenic mice with inducible cardiomyocyte-specific expression of calpain-2 were generated. An acute cardiotoxicity was induced in both transgenic mice and their relevant wild-type littermates by injection of a single dose of doxorubicin (20 mg/kg) and cardiac injury was analyzed 5 days after doxorubicin injection. Cardiomyocyte-specific up-regulation of calpain-2 did not induce any adverse cardiac phenotypes under physiological conditions by age 3 months, but significantly reduced myocardial injury and improved myocardial function in doxorubicin-treated mice. Cardiac protection of calpain-2 up-regulation was also observed in a mouse model of chronic doxorubicin cardiotoxicity. Up-regulation of calpain-2 increased the protein levels of mitogen activated protein kinase phosphatase-1 (MKP-1) in cultured mouse cardiomyocytes and heart tissues. Over-expression of MKP-1 prevented, whereas knockdown of MKP-1 augmented doxorubicin-induced apoptosis in cultured cardiomyocytes. Moreover, knockdown of MKP-1 offset calpain-2-elicited protective effects against doxorubicin-induced injury in cultured cardiomyocytes. Mechanistically, up-regulation of calpain-2 reduced the protein levels of phosphatase and tensin homolog and consequently promoted Akt activation, leading to increased MKP-1 protein steady-state levels by inhibiting its degradation. Collectively, this study reveals a new role of calpain-2 in promoting MKP-1 expression via phosphatase and tensin homolog/Akt signaling. This study also suggests that calpain-2/MKP-1 signaling may represent new therapeutic targets for doxorubicin-induced cardiac injury.
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