Interaction of Methylglyoxal and Hydrogen Sulfide in Rat Vascular Smooth Muscle Cells

Hydrogen sulfide (H2S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the effect of MG on H2S synthesis and the interaction between these two endogenous substances. In cultured vascular smooth muscle cells (VSMCs), MG (10, 30, and 50 mu M) significantly decreased cellular H2S levels in a concentration-dependent manner, while H2S donor, NaHS (30, 60, and 90 mu M), significantly decreased cellular MG levels. The expression level and activity of H2S-producing enzyme, cystathionine g-lyase (CSE), were significantly decreased by MG treatment. NaHS (30-90 mu M) significantly inhibited MG (10 or 30 mu M)-induced ROS production. Cellular levels of GSH, cysteine, and homocysteine were also increased by MG or NaHS treatment. Furthermore, direct reaction of H2S with MG in both concentration-and time-dependent manners were observed in in vitro incubations. In conclusion, MG regulates H2S level in VSMCs by downregulating CSE protein expression and directly reacting with H2S molecule. Interaction of MG with H2S may be one of future directions for the studies on glucose metabolism and the development of insulin resistance syndromes. Antioxid. Redox Signal. 12, 1093-1100.