Protective action of endogenously generated H2S on hypoxia-induced respiratory suppression and its relation to antioxidation and down-regulation of c-fos mRNA in medullary slices of neonatal rats

We previously reported that exogenous H2S played roles in protection of respiratory centers against hypoxic injury in medullary slices of neonatal rats. The protective action of endogenous H2S and its relation to antioxidation and down-regulation of c-fos mRNA were investigated in the present study. Perfusion of the slices with l-cysteine (Cys), substrate of cystathionine β-synthase (CBS, H2S synthase), could increase frequency of rhythmic respiratory discharge of the hypoglossal rootlets and prevent respiratory suppression induced by hypoxia, whereas perfusion with hydroxylamine (NH2OH, inhibitor of CBS) could postpone recovery of respiration from hypoxic inhibition. NH2OH also significantly enhanced hypoxia-induced increase in malondialdehyde (MDA) content of the slices. The hypoxia-induced up-regulation of c-fos mRNA could be markedly antagonized by S-adenosyl-l-methionine (SAM, activator of CBS), but greatly increased by NH2OH. Neither NH2OH, Cys nor SAM had any effect on expression of bcl-2 mRNA in hypoxic medullary slices. These results indicate that endogenously generated H2S was involved in protection of the medullary respiratory centers against hypoxic injury partly via antioxidation and down-regulation of c-fos.