Knockdown of Mtfp1 can minimize doxorubicin cardiotoxicity by inhibiting Dnm1l-mediated mitochondrial fission
- PMID: 28643438
- PMCID: PMC5706585
- DOI: 10.1111/jcmm.13250
Knockdown of Mtfp1 can minimize doxorubicin cardiotoxicity by inhibiting Dnm1l-mediated mitochondrial fission
Abstract
The long-term usage of doxorubicin (DOX) is largely limited due to the development of severe cardiomyopathy. Many studies indicate that DOX-induced cardiac injury is related to reactive oxygen species generation and ultimate activation of apoptosis. The role of novel mitochondrial fission protein 1 (Mtfp1) in DOX-induced cardiotoxicity remains elusive. Here, we report the pro-mitochondrial fission and pro-apoptotic roles of Mtfp1 in DOX-induced cardiotoxicity. DOX up-regulates the Mtfp1 expression in HL-1 cardiac myocytes. Knockdown of Mtfp1 prevents cardiac myocyte from undergoing mitochondrial fission, and subsequently reduces the DOX-induced apoptosis by preventing dynamin 1-like (Dnm1l) accumulation in mitochondria. In contrast, when Mtfp1 is overexpressed, a suboptimal dose of DOX can induce a significant percentage of cells to undergo mitochondrial fission and apoptosis. These data suggest that knocking down of Mtfp1 can minimize the cardiomyocytes loss in DOX-induced cardiotoxicity. Thus, the regulation of Mtfp1 expression could be a novel therapeutic approach in chemotherapy-induced cardiotoxicity.
Keywords: cardiotoxicity; doxorubicin; dyanmic-1-like (Dnm1l); mitochondrial fission; mitochondrial fission process 1 (Mtfp1).
© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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References
-
- De Iuliis F, Salerno G, Corvino R, et al Anthracycline‐free neoadjuvant chemotherapy ensures higher rates of pathologic complete response in breast cancer. Clin Breast Cancer. 2017; 1: 34–40. - PubMed
-
- Khaliq NU, Sandra FC, Park DY, et al Doxorubicin/heparin composite nanoparticles for caspase‐activated prodrug chemotherapy. Biomaterials. 2016; 101: 131–42. - PubMed
-
- Singal PK, Iliskovic N. Doxorubicin‐induced cardiomyopathy. N Engl J Med. 1998; 339: 900–5. - PubMed
-
- Rosen GM, Halpern HJ. Spin trapping biologically generated free radicals: correlating formation with cellular injury. Methods Enzymol. 1990; 186: 611–21. - PubMed
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