Upregulation of FAM129B protects cardiomyocytes from hypoxia/reoxygenation-induced injury by inhibiting apoptosis, oxidative stress, and inflammatory response via enhancing Nrf2/ARE activation.

Abstract

Family with sequence similarity 129, member B (FAM129B) has been identified as a novel cytoprotective protein that facilitates the survival of detrimentally stimulated cells. However, whether FAM129B is involved in regulating cardiomyocyte survival after myocardial ischemia-reperfusion injury is unknown. The goal of this work was to evaluate the potential role of FAM129B in regulating hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro. We demonstrated that exposure to H/R markedly downregulated the expression of FAM129B in cardiomyocytes. Functional experiments revealed that the upregulation of FAM129B improved H/R-exposed cardiomyocyte viability, and ameliorated H/R-induced cardiomyocyte apoptosis, the generation of reactive oxygen species (ROS), and pro-inflammatory cytokine release. The upregulation of FAM129B significantly increased the nuclear expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), and reinforced Nrf2/antioxidant response element (ARE) activation in H/R-exposed cardiomyocytes. Moreover, FAM129B modulates Nrf2/ARE signaling in a Kelchlike ECH-associated protein 1-dependent manner. Notably, the inhibition of Nrf2 significantly blocked FAM129B-overexpression-induced cardioprotective effects in H/R-exposed cardiomyocytes. In summary, the findings of our work demonstrate that the upregulation of FAM129B ameliorates H/R-induced cardiomyocyte injury via enhancing Nrf2/ARE activation. Thus, our study indicates that FAM129B may play a role in myocardial ischemia-reperfusion injury and has the potential to be used as a cardioprotective target.