| Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress. | |
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MedLine Citation:
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PMID: 20817827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Homocysteine, a cardiovascular and neurocognitive disease risk factor, is converted to hydrogen sulfide, a cardiovascular and neuronal protectant, through the transsulfuration pathway. Given the damaging effects of free homocysteine in the blood and the importance of blood homocysteine concentration as a prognosticator of disease, we tested the hypotheses that the blood itself regulates homocysteine-hydrogen sulfide metabolism through transsulfuration and that transsulfuration capacity and hydrogen sulfide availability protect the endothelium from redox stress. Here we show that the transsulfuration enzymes, cystathionine β-synthase and cystathionine γ-lyase, are secreted by microvascular endothelial cells and hepatocytes, circulate as members of the plasma proteome, and actively produce hydrogen sulfide from homocysteine in human blood. We further demonstrate that extracellular transsulfuration regulates cell function when the endothelium is challenged with homocysteine and that hydrogen sulfide protects the endothelium from serum starvation and from hypoxia-reoxygenation injury. These novel findings uncover a unique set of opportunities to explore innovative clinical diagnostics and therapeutic strategies in the approach to homocysteine-related conditions such as atherosclerosis, thrombosis, and dementia. |
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Authors:
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Shawn E Bearden; Richard S Beard; Jean C Pfau |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-09-03 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-11-29 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1568-76 Citation Subset: IM |
Affiliation:
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Idaho State Univ., Dept. of Biological Sciences, 921 S 8th Ave. Stop 8007, Pocatello, ID 83209-8007, USA. bearshaw@isu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Animals Cells, Cultured Cystathionine beta-Synthase / genetics, metabolism* Cystathionine gamma-Lyase / genetics, metabolism* Cysteine / metabolism Endothelium, Vascular / cytology, drug effects, metabolism* Hepatocytes / cytology, drug effects, metabolism Homocysteine / metabolism*, pharmacology Humans Hydrogen Sulfide / metabolism*, pharmacology Mice Mice, Inbred C57BL Middle Aged Models, Animal Oxidation-Reduction Oxidative Stress / drug effects, physiology* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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P20 RR-016454/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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454-28-4/Homocysteine; 52-90-4/Cysteine; 7783-06-4/Hydrogen Sulfide; EC 4.2.1.22/Cystathionine beta-Synthase; EC 4.4.1.1/Cystathionine gamma-Lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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