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TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy.
Biochim Biophys Acta Mol Basis Dis. 2018 May; 1864(5 Pt A):1728-1743.BB

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 effects of TAX1BP1 in cardiomyocytes. TAX1BP1 thus restores the decreased autophagy level, leading to decreased inflammatory responses and oxidative stress and reduced apoptosis in cardiomyocytes.

Authors+Show Affiliations

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. Electronic address: qztang@whu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29476905

Citation

Xiao, Yang, et al. "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, vol. 1864, no. 5 Pt A, 2018, pp. 1728-1743.
Xiao Y, Wu QQ, Duan MX, et al. TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt A):1728-1743.
Xiao, Y., Wu, Q. Q., Duan, M. X., Liu, C., Yuan, Y., Yang, Z., Liao, H. H., Fan, D., & Tang, Q. Z. (2018). 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, 1864(5 Pt A), 1728-1743. https://doi.org/10.1016/j.bbadis.2018.02.012
Xiao Y, et al. TAX1BP1 Overexpression Attenuates Cardiac Dysfunction and Remodeling in STZ-induced Diabetic Cardiomyopathy in Mice By Regulating Autophagy. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt A):1728-1743. PubMed PMID: 29476905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy. AU - Xiao,Yang, AU - Wu,Qing Qing, AU - Duan,Ming Xia, AU - Liu,Chen, AU - Yuan,Yuan, AU - Yang,Zheng, AU - Liao,Hai Han, AU - Fan,Di, AU - Tang,Qi Zhu, Y1 - 2018/02/21/ PY - 2017/11/22/received PY - 2018/02/03/revised PY - 2018/02/19/accepted PY - 2018/2/25/pubmed PY - 2018/7/10/medline PY - 2018/2/25/entrez KW - Autophagy KW - Diabetic cardiomyopathy KW - Non-canonical NF-κB KW - RelB KW - Tax1 binding protein 1 SP - 1728 EP - 1743 JF - Biochimica et biophysica acta. Molecular basis of disease JO - Biochim Biophys Acta Mol Basis Dis VL - 1864 IS - 5 Pt A N2 - 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 effects of TAX1BP1 in cardiomyocytes. TAX1BP1 thus restores the decreased autophagy level, leading to decreased inflammatory responses and oxidative stress and reduced apoptosis in cardiomyocytes. SN - 0925-4439 UR - https://www.unboundmedicine.com/medline/citation/29476905/TAX1BP1_overexpression_attenuates_cardiac_dysfunction_and_remodeling_in_STZ_induced_diabetic_cardiomyopathy_in_mice_by_regulating_autophagy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(18)30069-3 DB - PRIME DP - Unbound Medicine ER -