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Tripartite motif-containing protein 16 protects against myocardial ischemia/reperfusion injury by affecting the Keap1/Nrf2 axis

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Abstract

Tripartite motif-containing protein (TRIM16) is a newly identified oxidative-stress-responsive protein. Oxidative stress is a hallmark of myocardial ischemia/reperfusion (I/R) injury and contributes to the cardiac injury. To date, whether TRIM16 plays a role in mediating oxidative stress during myocardial I/R injury is undetermined. The work is devoted to evaluate the possible relevance of TRIM16 in myocardial I/R injury. TRIM16 induction by myocardial hypoxia/reoxygenation (H/R) injury in vitro or myocardial I/R injury in vivo was observed. TRIM16 overexpression alleviated H/R-induced injury of rat cardiomyocytes. TRIM16 overexpression markedly attenuated cardiac injury, infarct size, and myocardial apoptosis induced by myocardial I/R injury. Further research revealed that TRIM16 was capable of enhancing Nrf2 activation via the regulation of Keap1. The inhibition of Nrf2 diminished TRIM16-overexpression-mediated cardioprotective effects. Overall, this work demonstrates that TRIM16 protects against myocardial I/R injury via affecting the Keap1/Nrf2 axis. This work offers new insights into the molecular mechanism underlying myocardial I/R injury and proposes TRIM16 as an attractive candidate target for cardioprotection.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an 710068, China

    Qianwei Cui & Li Yan

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  1. Qianwei Cui
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  2. Li Yan
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Correspondence to Li Yan.

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

Research involving human participants and/or animals

The animal use for the study was approved by the Ethics Committee of Shaanxi Provincial People’s Hospital, and the animal care and protocol were carried out in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, revised 1996).

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Cui, Q., Yan, L. Tripartite motif-containing protein 16 protects against myocardial ischemia/reperfusion injury by affecting the Keap1/Nrf2 axis. Cell Tissue Res 386, 349–363 (2021). https://doi.org/10.1007/s00441-021-03518-4

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