Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
H2S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine -Lyase
Guangdong Yang,1,5Lingyun Wu,2*Bo Jiang,1Wei Yang,1Jiansong Qi,1Kun Cao,1Qinghe Meng,3Asif K. Mustafa,4Weitong Mu,4,6Shengming Zhang,5Solomon H. Snyder,4*Rui Wang1,5*
Studies of nitric oxide over the past two decades have highlightedthe fundamental importance of gaseous signaling molecules inbiology and medicine. The physiological role of other gasessuch as carbon monoxide and hydrogen sulfide (H2S) is now receivingincreasing attention. Here we show that H2S is physiologicallygenerated by cystathionine -lyase (CSE) and that genetic deletionof this enzyme in mice markedly reduces H2S levels in the serum,heart, aorta, and other tissues. Mutant mice lacking CSE displaypronounced hypertension and diminished endothelium-dependentvasorelaxation. CSE is physiologically activated by calcium-calmodulin,which is a mechanism for H2S formation in response to vascularactivation. These findings provide direct evidence that H2Sis a physiologic vasodilator and regulator of blood pressure.
1 Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. 2 Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. 3 Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. 4 Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 5 Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada. 6 Department of Medicine, Gastroenterology Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
* To whom correspondence should be addressed. E-mail: rwang{at}lakeheadu.ca (R.W.), lily.wu{at}usask.ca (L.W.), or ssnyder{at}jhmi.edu (S.H.S.).
The editors suggest the following Related Resources on Science sites:
In Science Signaling
EDITORS' CHOICE
Paula A. Kiberstis (28 October 2008) Sci. Signal.1 (43), ec367.
[DOI: 10.1126/scisignal.143ec367] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Science Signaling Podcast: 10 November 2009.
S. H. Snyder and A. M. VanHook (2009)
Science Signaling
2, pc20
|Abstract »|Full Text »
H2S Signals Through Protein S-Sulfhydration.
A. K. Mustafa, M. M. Gadalla, N. Sen, S. Kim, W. Mu, S. K. Gazi, R. K. Barrow, G. Yang, R. Wang, and S. H. Snyder (2009)
Science Signaling
2, ra72
|Abstract »|Full Text »|PDF »
Vascular Endothelium Expresses 3-Mercaptopyruvate Sulfurtransferase and Produces Hydrogen Sulfide.
N. Shibuya, Y. Mikami, Y. Kimura, N. Nagahara, and H. Kimura (2009)
J. Biochem.
146, 623-626
|Abstract »|Full Text »|PDF »
Neurotransmitters, Receptors, and Second Messengers Galore in 40 Years.
No facilitator required for membrane transport of hydrogen sulfide.
J. C. Mathai, A. Missner, P. Kugler, S. M. Saparov, M. L. Zeidel, J. K. Lee, and P. Pohl (2009)
PNAS
106, 16633-16638
|Abstract »|Full Text »|PDF »
Relative Contributions of Cystathionine {beta}-Synthase and {gamma}-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions.
S. Singh, D. Padovani, R. A. Leslie, T. Chiku, and R. Banerjee (2009)
J. Biol. Chem.
284, 22457-22466
|Abstract »|Full Text »|PDF »
Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.
A. F. Perna, M. G. Luciano, D. Ingrosso, P. Pulzella, I. Sepe, D. Lanza, E. Violetti, R. Capasso, C. Lombardi, and N. G. De Santo (2009)
Nephrol. Dial. Transplant.
|Abstract »|Full Text »|PDF »
U. Sen, P. Basu, O. A. Abe, S. Givvimani, N. Tyagi, N. Metreveli, K. S. Shah, J. C. Passmore, and S. C. Tyagi (2009)
Am J Physiol Renal Physiol
297, F410-F419
|Abstract »|Full Text »|PDF »
Ischemia-reperfusion reduces cystathionine-{beta}-synthase-mediated hydrogen sulfide generation in the kidney.
Z. Xu, G. Prathapasinghe, N. Wu, S.-Y. Hwang, Y. L. Siow, and K. O (2009)
Am J Physiol Renal Physiol
297, F27-F35
|Abstract »|Full Text »|PDF »
Embryonic temperature affects muscle fibre recruitment in adult zebrafish: genome-wide changes in gene and microRNA expression associated with the transition from hyperplastic to hypertrophic growth phenotypes.
I. A. Johnston, H.-T. Lee, D. J. Macqueen, K. Paranthaman, C. Kawashima, A. Anwar, J. R. Kinghorn, and T. Dalmay (2009)
J. Exp. Biol.
212, 1781-1793
|Abstract »|Full Text »|PDF »
Role of hydrogen sulfide in visceral nociception.
M. Schemann and D. Grundy (2009)
Gut
58, 744-747
|Full Text »|PDF »
Blood pressure control: hydrogen sulfide, a new gasotransmitter, takes stage.
C. Zoccali, C. Catalano, and S. Rastelli (2009)
Nephrol. Dial. Transplant.
24, 1394-1396
|Full Text »|PDF »
Signaling by Gasotransmitters.
A. K. Mustafa, M. M. Gadalla, and S. H. Snyder (2009)
Science Signaling
2, re2
|Abstract »|Full Text »|PDF »
H2S Biogenesis by Human Cystathionine {gamma}-Lyase Leads to the Novel Sulfur Metabolites Lanthionine and Homolanthionine and Is Responsive to the Grade of Hyperhomocysteinemia.
T. Chiku, D. Padovani, W. Zhu, S. Singh, V. Vitvitsky, and R. Banerjee (2009)
J. Biol. Chem.
284, 11601-11612
|Abstract »|Full Text »|PDF »
Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation.
R. d'Emmanuele di Villa Bianca, R. Sorrentino, P. Maffia, V. Mirone, C. Imbimbo, F. Fusco, R. De Palma, L. J. Ignarro, and G. Cirino (2009)
PNAS
106, 4513-4518
|Abstract »|Full Text »|PDF »
R. Wang (2009)
Arterioscler Thromb Vasc Biol
29, 156-157
|Full Text »|PDF »
Structural Basis for the Inhibition Mechanism of Human Cystathionine {gamma}-Lyase, an Enzyme Responsible for the Production of H2S.
Q. Sun, R. Collins, S. Huang, L. Holmberg-Schiavone, G. S. Anand, C.-H. Tan, S. van-den-Berg, L.-W. Deng, P. K. Moore, T. Karlberg, et al. (2009)
J. Biol. Chem.
284, 3076-3085
|Abstract »|Full Text »|PDF »
Vascular Tone Is Influenced by Another Gas: Hydrogen Sulfide.
(2008)
Journal Watch (General)
2008, 5
|Full Text »
-Lyase
-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure. 
