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

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.