Abstract
BackgroundThe poliferation of vascular smooth muscle cells (VSMCs) is the main cause of diabetic vascular complications. Hydrogen sulfide (H2S), a gaseous molecule, is involved in modulating multiple physiological functions. H2S could inhibit VSMCs proliferation induced by hyperglycemia and hyperlipidemia, however, the mechanisms are unclear. ResultsOur results showed that H2S level was lower and expression of proliferative protein for PCNA and CyclinD1 was higher in db/db mice aorta and VSMC treated by glucose and palmitate, whereas, exogenous H2S decreased PCNA and CyclinD1 expression. We found that mitochondrial pyruvate dehydrogenase complex-E1 (PDC-E1) was significantly translocated to the nucleus of VSMCs with the treatment of high glucose and palmitate, and it increased the level of acetyl-CoA and histone acetylation (H3K9Ac). Exogenous H2S inhibited PDC-E1 translocation from mitochondria to nucleus, due to PDC-E1 being modified via S-sulfhydration. In addition, PDC-E1 was mutated at Cys101. Overexpression of PDC-E1 mutated at Cys101 enhanced histone acetylation (H3K9Ac) and VSMCs proliferation.ConclusionsThese findings suggested that H2S regulated PDC-E1 S-sulfhydration at Cys101 to prevent its translocation from mitochondria to nucleus and inhibit VSMCs proliferation in diabetic conditions.