Document Detail


Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide.
MedLine Citation:
PMID:  19631409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hydrogen sulfide (H(2)S) is an essential physiological product in brain. We investigated the expression of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CGL), the two H(2)S synthesizing enzymes, in human cell lines and in human brain. Only astrocytes were strongly immunostained for CBS. Cultured astrocytes synthesized H(2)S at the rate of 15.06 micromol/g protein/h, which was 7.57 fold higher than microglial cells, 10.27 fold higher than SH-SY5Y cells and 11.32 fold higher than NT-2 cells. The H(2)S synthesis in all these cell types was inhibited by the CBS inhibitor hydroxylamine, but not by the CGL inhibitor propargylglycine (PAG). Synthesis of H(2)S by HUVEC cells was inhibited by PAG but not by hydroxylamine indicating that these vascular cells utilize CGL but not CBS. Inflammatory activation of microglia and astrocytes caused induction of NFkappaB, release of the inflammatory mediators TNFalpha, IL-6 and nitrite ions, down-regulation of CBS, and down-regulation of H(2)S synthesis. There was no effect of such treatment on HUVEC cells. The effects were partially reversed by pretreatment of cells with the H(2)S releasing agent NaSH. These data indicate that H(2)S is an endogenous antiinflammatory and neuroprotective agent under the synthetic control of CBS. H(2)S releasing drugs may have therapeutic potential in neurodegenerative disorders of aging such as Alzheimer disease and Parkinson disease.
Authors:
Moonhee Lee; Claudia Schwab; Sheng Yu; Edith McGeer; Patrick L McGeer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-23
Journal Detail:
Title:  Neurobiology of aging     Volume:  30     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-10-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1523-34     Citation Subset:  IM    
Affiliation:
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Alkynes / pharmacology
Astrocytes / enzymology,  immunology,  metabolism*
Brain / enzymology,  immunology,  metabolism*
Cell Line, Tumor
Cells, Cultured
Cystathionine beta-Synthase / antagonists & inhibitors,  metabolism
Cystathionine gamma-Lyase / antagonists & inhibitors,  metabolism
Enzyme Inhibitors / pharmacology
Female
Glycine / analogs & derivatives,  pharmacology
Humans
Hydrogen Sulfide / metabolism*
Hydroxylamine / pharmacology
Interleukin-6 / metabolism
Male
Microglia / enzymology,  immunology,  metabolism
NF-kappa B / metabolism
Neuroprotective Agents / metabolism*
Nitrites / metabolism
Tumor Necrosis Factor-alpha / metabolism
Chemical
Reg. No./Substance:
0/Alkynes; 0/Enzyme Inhibitors; 0/IL6 protein, human; 0/Interleukin-6; 0/NF-kappa B; 0/Neuroprotective Agents; 0/Nitrites; 0/Tumor Necrosis Factor-alpha; 56-40-6/Glycine; 64165-64-6/propargylglycine; 7783-06-4/Hydrogen Sulfide; 7803-49-8/Hydroxylamine; 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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