Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells.
Bottom Line: Their interaction at different levels would have a profound impact on angiogenesis.Blockade of NO production by eNOS-specific siRNA or nitro-L-arginine methyl ester (L-NAME) reversed, but eNOS overexpression potentiated, the proliferative effect of H2 S on ECs.Our results suggest that H2 S stimulates the phosphorylation of eNOS through a p38 MAPK and Akt-dependent pathway, thus increasing NO production in ECs and vascular tissues and contributing to H2 S-induced angiogenesis.
Affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.Show MeSH
Mentions: Diverse kinases such as Akt, p38-MAPK kinase and ERK are important for NO production and signalling activation 25â€“27. To elucidate the signalling pathways involved in H2S-induced eNOS phosphorylation and the NO production, we examined the roles of Akt, ERK and p38 MAPK in H2S-stimulated NO production. Treatment with NaHS at 100 Î¼M enhanced the phosphorylation of p38 MAPK, Akt and ERK to different levels (Fig. 3). SB202190 (a p38 MAPK inhibitor) and LY294002 (a PI3K/Akt inhibitor), but not U0126 (an inhibitor of ERK), significantly reduced H2S-induced phosphorylation of eNOS (Fig. 4). We further found that the stimulatory effect of NaHS on NO production was decreased by the same treatments (SB202190 or LY294002), and neither SB202190 nor LY294002 alone had any detectable effect on NO production (Fig. 5A). In addition, p38 MAPK inhibition by SB202190 attenuated the NaHS-induced phosphorylation of Akt (Fig. 5B), indicating that p38 MAPK might regulate the upstream signalling cascade that leads to Akt activation. These results suggest that p38 MAPK and Akt are required for NO activation by H2S.
Affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.