Tom70 protects against diabetic cardiomyopathy through its antioxidant and antiapoptotic properties.

Peijian Wang, Dan Wang, Yi Yang, Jixin Hou, Jindong Wan, Fei Ran, Xiaozhen Dai, Peng Zhou, Yongjian Yang

Hypertension research : official journal of the Japanese Society of Hypertension 2020 Oct

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Mitochondrial dysfunction plays a critical role in the pathogenesis of diabetic cardiomyopathy. Translocase of mitochondrial outer membrane 70 (Tom70) primarily facilitates the import of mitochondrial preproteins that may be involved in the regulation of oxidative stress and mitochondrial function. This study aimed to investigate the role of Tom70 in the development of myocardial injury in leptin receptor-deficient (db/db) diabetic mice. Tom70 siRNA or an overexpressing lentivirus was intramuscularly injected into mouse hearts or used to treat cultured neonatal cardiomyocytes. We found that Tom70 was downregulated in the diabetic hearts compared with the level in the wild-type hearts and that knocking down Tom70 exacerbated cardiac hypertrophy, fibrosis, and ventricular dysfunction in the db/db mice. Similarly, the in vitro data demonstrated that silencing Tom70 enhanced high-glucose and high-fat (HGHF) medium treatment-induced mitochondrial superoxide production, decreased ATP production and the mitochondrial membrane potential, and enhanced cell apoptosis in neonatal cardiomyocytes. Importantly, overexpression of Tom70 alleviated HGHF medium-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Furthermore, in vivo data confirmed that reconstitution of Tom70 ameliorated cardiac hypertrophy, interstitial fibrosis, and ventricular dysfunction in the db/db mice. In addition, Tom70 overexpression mitigated mitochondrial fragmentation and dysfunction in the hearts of the db/db mice. Taken together, these findings suggest that downregulation of Tom70 contributes to the development of diabetic cardiomyopathy and that reconstitution of Tom70 may be a new therapeutic strategy for the prevention and treatment of diabetic cardiomyopathy.

Citation

Peijian Wang, Dan Wang, Yi Yang, Jixin Hou, Jindong Wan, Fei Ran, Xiaozhen Dai, Peng Zhou, Yongjian Yang. Tom70 protects against diabetic cardiomyopathy through its antioxidant and antiapoptotic properties. Hypertension research : official journal of the Japanese Society of Hypertension. 2020 Oct;43(10):1047-1056