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Ubiquitin-Specific Protease 10 Suppresses Cardiac Hypertrophy by Inhibiting Sirt6

36 Pages Posted: 16 Oct 2019

See all articles by Dian-Hong Zhang

Dian-Hong Zhang

Zhengzhou University - Cardiovascular Hospital

Jie-Lei Zhang

Zhengzhou University

Zhen Huang

Zhengzhou University - Cardiovascular Hospital

Lei-Ming Wu

Zhengzhou University - Cardiovascular Hospital

Zhong-min Wang

FuWai Central China Cardiovascular Hospital

Ya-Peng Li

Zhengzhou University - Cardiovascular Hospital

Xin-Yu Tian

Zhengzhou University - Cardiovascular Hospital

Ling-Yao Kong

Zhengzhou University - Cardiovascular Hospital

Rui Yao

Zhengzhou University - Cardiovascular Hospital

Yanzhou Zhang

Zhengzhou University - Cardiovascular Hospital

More...

Abstract

Background and Purpose: Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can evolve to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. Ubiquitin-specific protease 10 (USP10) is a member of the ubiquitin-specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 in CH.

Experimental Approach: In this study, by utilizing conditional cardiac-specific USP10 knockout (USP10-CKO) mice and USP10- transgenic(USP10-TG) mice, we examined the role of USP10 in hypertrophic hearts. We further examined the specific function of USP10 in cardiomyocytes.

Key Results: We show that USP10 expression increased in murine hypertrophic hearts. Mice deficient in USP10 in the heart exhibited an aggravated aortic banding (AB)-induced CH phenotype. However, overexpression of USP10 protected against pressure overload-induced hypertrophy. At the molecular level, the prevention of CH in the absence of USP10 involves elevated Akt pathway components, which are key elements that regulate cell apoptosis and proliferation. Moreover, USP10 physically binds to Sirt6 and inhibits Akt phosphorylation.

Conclusion and Implications: These observations demonstrate that USP10 functions as a positive switch in CH.

Funding Statement: This work was supported by grants from National Natural Science Foundation of China (81770048;81970242); Cooperative Project of Academy training Foundation of Zhengzhou University(2016-BSTDJJ-13).

Declaration of Interests: The authors stated: "None."

Ethics Approval Statement: All animal use protocols were approved by the Animal Care and Use Committee of The First Affiliated Hospital of Zhengzhou University. The related procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Keywords: Ubiquitin-Specific Protease 10; Cardiac Hypertrophy; Sirt6; Akt

Suggested Citation

Zhang, Dian-Hong and Zhang, Jie-Lei and Huang, Zhen and Wu, Lei-Ming and Wang, Zhong-min and Li, Ya-Peng and Tian, Xin-Yu and Kong, Ling-Yao and Yao, Rui and Zhang, Yanzhou, Ubiquitin-Specific Protease 10 Suppresses Cardiac Hypertrophy by Inhibiting Sirt6 (October 11, 2019). Available at SSRN: https://ssrn.com/abstract=3468371 or http://dx.doi.org/10.2139/ssrn.3468371

Dian-Hong Zhang

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Jie-Lei Zhang

Zhengzhou University

100 Science Avenue
Zhengzhou, Henan 450001
China

Zhen Huang

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Lei-Ming Wu

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Zhong-min Wang

FuWai Central China Cardiovascular Hospital

Zhengzhou
China

Ya-Peng Li

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Xin-Yu Tian

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Ling-Yao Kong

Zhengzhou University - Cardiovascular Hospital

Zhengzhou
China

Rui Yao

Zhengzhou University - Cardiovascular Hospital ( email )

Zhengzhou
China

Yanzhou Zhang (Contact Author)

Zhengzhou University - Cardiovascular Hospital ( email )

Zhengzhou
China

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