H2S, un nouveau neuromodulateur H2S, a new neuromodulator

Résumé

Le sulfure d’hydrogène (H₂S) est produit dans de nombreux tissus, et notamment dans le cerveau, où il joue un rôle de neuromodulateur. H₂S augmente ainsi les réponses mises en jeu par les récepteurs NMDA et facilite l’induction d’une potentialisation à long terme dans l’hippocampe. L’altération de la concentration de l’activateur physiologique de la cystathionine β synthase, enzyme responsable de la synthèse d’H₂S dans le cerveau, explique la diminution de la concentration d’H₂S dans les cerveaux de sujets atteints de maladie d’Alzheimer. L’hyperproduction d’H₂S décrite chez les sujets trisomiques 21 est probablement liée à l’hyperexpression de cette même enzyme, dont le gène est localisé sur le chromosome 21.

Summary

The formation of H₂S from cyst(e)ine is catalyzed by three enzymes, cystathionine β synthase, cystathionase, and 3-mercaptopyruvate sulfurtransferase. In the liver, kidney, enterocytes and vascular smooth muscle cells, H₂S is principally synthesized by cystathionase. In contrast, it is synthesized by cystathionine β synthase in the brain and partially by 3-mercaptopyruvate sulfurtransferase in cardiac tissue. H₂S is catabolized, essentially in mitochondria by thiosulfate reductase. The sulfite generated is then oxidized to sulfate by sulfite oxidase. The amount of thiosulfate excreted in the urine is the best indicator of H₂S biosynthesis, together with sulfhemoglobin determination in erythrocytes. H₂S acts as a neuromodulator in the brain, increasing responses mediated by NMDA receptors, facilitating the induction of long-term potentialization in the hippocampus. H₂S also acts as a vasodilator, acting directly on ATP-dependent potassium channels in vascular smooth muscle cells. The concentration of H₂S is abnormally low in the brains of subjects with Alzheimer’s disease, due to changes in the concentration of the physiological activator of cystathionine β synthase. The overproduction of H₂S described in subjects with Down’s syndrome probably results from the overproduction of cystathionine β synthase, as the gene encoding this protein is located on chromosome 21.