Inhibition of SF3A2 acetylation at lysine 10 mediated by p300/SIRT7 promotes Fscn1 alternative splicing against myocardial ischemic/reperfusion injury [RNA-Seq I]
The 4D-lable free proteomic and acetylomic study were employed to gain the targets of GS. The co-immunoprecipitation, co-localization, and specific acetylation site antibody were used to verify the acetylation. Based on the mass spectrometry analysis, the active monomers in GS were screened by phenotypes of acetylation and mitochondrial function. The mechanism was studied through RNA-seq, qPCR, cellular thermal shift assay, surface plasmon resonance, acetyltransferase activity combined with pharmacological inhibitor, RNA interference and site-specific mutation. These findings provide a novel mechanism underlying cardiomyocyte protection of ginsenoside Rb2 through p300/SIRT7-SF3A2-Fscn1 signaling and opens new opportunities for pharmacological prevention and treatment of ischemic and associated sequelae. Overall design: H9C2 cells were pretreated with ginsenoside Rb2 for 48h, and then treated with glucose-oxygen deprivation in a three-gas incubator for 4-6 h, and reoxygenated with glucose-reoxygenation for 12 h.