Involvement of redox-signalling in endogenous hydrogen sulfide production.

UNLABELLED: Recently, cystathionine-γ-lyase (CSE) was found to provide the major physiological pathway for H(2) S, the third member of the gasotransmitter family. In various pathophysiological conditions, H(2) S exerted protective effects based on its antioxidant, anti-inflammatory, anti-hypertensive and other regulatory functions. Interestingly, CSE expression had been only poorly studied and only in relation with inflammatory processes. Therefore, the study by Hassan et al. in this issue of the BJP, provides a considerable advance by furnishing direct experimental evidence for the involvement of redox signalling in the regulation of CSE gene expression. They found that PDGF up-regulated CSE expression and activity that was abolished by antioxidants and by deletion of the transcription factor nuclear erythroid-2-related factor-2 (Nrf2). Furthermore, PDGF induced Nrf2 binding to its consensus sequence that was again reversed by antioxidants. As Nrf2 also governs CO biosynthesis, and PDGF inversely affects H(2) S and NO production, these data could indicate a concerted regulation of the three gasotransmitters by redox signalling. LINKED ARTICLE: This article is a commentary on Hassan et al., pp. 2231-2242 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01949.x.