O-GlcNAc transferase-mediated O-GlcNAcylation of CD36 against myocardial ischemia-reperfusion injury

CD36 affects lipid metabolism and is involved in the development of myocardial infarction (MI). O-GlcNAcylation is a promising therapeutic target for myocardial ischemia-reperfusion (I/R) injury. This study aimed to investigate the effects of CD36 on myocardial I/R injury and its O-GlcNAcylation. H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and phenotypes were evaluated using cell counting kit-8, EdU assay, flow cytometry, and TUNEL assay. The O-GlcNAcylation was evaluated by immunoprecipitation, immunoblotting, and cycloheximide chase assay. The role of CD36 in vivo was analyzed by TTC staining and TUNEL assay. The results showed that CD36 protein levels were downregulated in I/R rats and H/R-induced H9C2 cells. OGT and O-GlcNAcylation levels were decreased by H/R. Overexpression of CD36 or OGT promoted cell proliferation and inhibited Apoptosis of H/R-treated cells. Moreover, OGT facilitated the O-GlcNAcylation of CD36 at S195 site and enhanced CD36 protein stability. Knockdown of CD36 abrogated the effects of cellular behaviors caused by OGT, and CD36 mutation at S195 site reversed the promotion of proliferation and lipid uptake and the inhibition of Apoptosis induced by wild-type CD36. Additionally, overexpression of CD36 attenuated infarction and Apoptosis in the myocardium of rats. In conclusion, OGT-mediated O-GlcNAcylation of CD36 attenuates myocardial I/R injury through promoting the proliferation and inhibiting Apoptosis of cardiomyocytes. The findings suggest that targeting CD36 O-GlcNAcylation may be a promising therapy for MI.

CD36; Hypoxia/reoxygenation; Myocardial ischemia-reperfusion injury; O-GlcNAcylation; OGT.