Research Paper Volume 12, Issue 24 pp 25452—25468

Sevoflurane postconditioning reduces myocardial ischemia reperfusion injury-induced necroptosis by up-regulation of OGT-mediated O-GlcNAcylated RIPK3

Figure 7. Schematic diagram depicting the role of OGT mediated O-GlcNAcylation and necroptosis signaling in the SPC induced cardioprotective effect on MIRI. MIRI could induce the up-regulation of RIPK1/RIPK3/MLKL axis mediated necroptosis. And SPC promoted the increase of OGT induced O-GlcNAcylation, enhanced the RIPK3 O-GlcNAcylation, and then inhibited the formation of the RIPK3/MLKL complex, finally lead to the inhibition of MIRI mediated necroptosis. Furthermore, the protective effects of SPC against MIRI was abrogated by using the OGT inhibitor OSMI-1. In brief, SPC restrained cardiomyocytes necroptosis via regulating OGT mediated O-GlcNAcylation of RIPK3 and lessening RIPK3/MLKL induced necroptosis, and hence protected the heart against MIRI.