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

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.