TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Yang XiaoQi Zhu Tang

Abstract

Diabetic cardiomyopathy is associated with suppressed autophagy and augmented inflammation in the heart. The effects of Tax1 binding protein 1 (TAX1BP1) on both autophagy and inflammation suggest that it may participate in the progression of diabetic cardiomyopathy. Mice were injected with streptozotocin (STZ) to induce experimental diabetes. An adenovirus system was used to induce heart specific TAX1BP1 overexpression 12 weeks after STZ injection. TAX1BP1 expression was significantly decreased in STZ-induced diabetic mouse hearts. TAX1BP1 overexpression in the heart alleviated cardiac hypertrophy and fibrosis, attenuated inflammation, oxidative stress, and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Diabetic mice exhibited decreased autophagy. By contrast, increased autophagy was observed in diabetic mice overexpressing TAX1BP1. TAX1BP1 overexpression promoted autophagic flux, as demonstrated by increased LC3-RFP fluorescence in vitro. Furthermore, the autophagy inhibitor 3-MA abolished the protective effects of TAX1BP1 in vivo. Interestingly, we found that TAX1BP1 increased autophagy via the activation of a non-canonical NF-κB signaling pathway. Conversely, RelB knockdown disrupted the protective ef...Continue Reading

Citations

Feb 1, 2019·Journal of Cellular and Molecular Medicine·Leilei YinXinhua Yin
Nov 30, 2018·Frontiers in Cell and Developmental Biology·Vartika SharmaDhiraj Kumar
Aug 28, 2020·Free Radical Biology & Medicine·Ning LiQizhu Tang
Apr 11, 2021·Ageing Research Reviews·Saikat DewanjeeRamesh Kandimalla

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