Hydrogen Sulfide Is Produced in Response to Neuronal Excitation

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain. Physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and alter the induction of hippocampal long-term potentiation (LTP). Here we use cystathionine β-synthase (CBS) knock-out mice to clearly show that CBS produces endogenous H2S in the brain and that H2S production is greatly enhanced by the excitatory neurotransmitterl-glutamate, as well as by electrical stimulation. This increased CBS activity is regulated by a pathway involving Ca2+/calmodulin. In addition, LTP is altered in CBS knock-out mice. These observations suggest that H2S is produced by CBS in response to neuronal excitation and that it may regulate some aspects of synaptic activity.

[1]  A. Pick,et al.  Activation of cystathionine synthase by adenosylmethionine and adenosylethionine. , 1975, Biochemical and biophysical research communications.

[2]  Roland L. Dunbrack,et al.  Mutations in the regulatory domain of cystathionine beta synthase can functionally suppress patient-derived mutations in cis. , 2001, Human molecular genetics.

[3]  D. Gould,et al.  Determination of sulfide in brain tissue and rumen fluid by ion-interaction reversed-phase high-performance liquid chromatography. , 1990, Journal of chromatography.

[4]  D. Linden,et al.  Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse. , 1998, Journal of neurophysiology.

[5]  M. Stipanuk,et al.  Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. , 1982, The Biochemical journal.

[6]  R. Llinás The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. , 1988, Science.

[7]  D. Madison,et al.  A requirement for the intercellular messenger nitric oxide in long-term potentiation. , 1991, Science.

[8]  Charles F. Stevens,et al.  Reversal of long-term potentiation by inhibitors of haem oxygenase , 1993, Nature.

[9]  J. Kraus,et al.  Transsulfuration depends on heme in addition to pyridoxal 5'-phosphate. Cystathionine beta-synthase is a heme protein. , 1994, The Journal of biological chemistry.

[10]  S. Mudd Disorders of transsulfuration , 1989 .

[11]  A. Rhoads,et al.  Sequence motifs for calmodulin recognition , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  N. Maeda,et al.  Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  H. Kimura Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. , 2000, Biochemical and biophysical research communications.

[14]  S. Snyder,et al.  Atypical neural messengers , 2001, Trends in Neurosciences.

[15]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[16]  John Garthwaite,et al.  On the Role of Nitric Oxide in Hippocampal Long-Term Potentiation , 2003, The Journal of Neuroscience.

[17]  K. Abe,et al.  The possible role of hydrogen sulfide as an endogenous neuromodulator , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  Preziosi,et al.  Evidence That Hydrogen Sulphide Can Modulate Hypothalamo‐Pituitary‐Adrenal Axis Function: In Vitro and In Vivo Studies in the Rat , 2000, Journal of neuroendocrinology.

[19]  M. Maines Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications , 1988, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  J. Kraus,et al.  Trypsin cleavage of human cystathionine beta-synthase into an evolutionarily conserved active core: structural and functional consequences. , 1998, Archives of biochemistry and biophysics.

[21]  E. Kandel,et al.  Nitric oxide and carbon monoxide produce activity-dependent long-term synaptic enhancement in hippocampus. , 1993, Science.

[22]  E. Kandel,et al.  Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[23]  S. Roth,et al.  Toxicology of hydrogen sulfide. , 1992, Annual review of pharmacology and toxicology.

[24]  M. Swaroop,et al.  Rat cystathionine beta-synthase. Gene organization and alternative splicing. , 1992, Journal of Biological Chemistry.

[25]  J. Taylor,et al.  Determination of sulfide in brain tissue by gas dialysis/ion chromatography: postmortem studies and two case reports. , 1989, Journal of analytical toxicology.

[26]  Y. Hoshika,et al.  Gas chromatographic determination of sulphur compounds in town gas. , 1977, Journal of chromatography.

[27]  O. Griffith Mammalian sulfur amino acid metabolism: an overview. , 1987, Methods in enzymology.

[28]  S. Snyder,et al.  Carbon monoxide: a putative neural messenger. , 1993, Science.

[29]  J. Garthwaite,et al.  Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain , 1988, Nature.

[30]  S. Moncada,et al.  Vascular endothelial cells synthesize nitric oxide from L-arginine , 1988, Nature.

[31]  J. Taylor,et al.  Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. , 1989, Biochemical pharmacology.

[32]  S. Snyder,et al.  Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.