H2S, un nouveau neuromodulateur

H2S, a new neuromodulator

Laboratoire de Biochimie médicale B, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France

^* pierre.kamoun@nck.ap-hop-paris.fr

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 bêta 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.

Abstract

The formation of H2S from cyst(e)ine is catalyzed by three enzymes, cystathionine bêta 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 bêta 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 bêta synthase. The overproduction of H2S described in subjects with Down’s syndrome probably results from the overproduction of cystathionine bêta synthase, as the gene encoding this protein is located on chromosome 21.