Document Detail


Induction of S100B secretion in C6 astroglial cells by the major metabolites accumulating in glutaric acidemia type I.
MedLine Citation:
PMID:  20437086     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glutaryl-CoA dehydrogenase deficiency or glutaric acidemia type I (GA I) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3OHGA) acids and clinically by severe neurological symptoms and structural brain abnormalities, manifested as progressive cerebral atrophy and acute striatum degeneration following encephalopathic crises, whose pathophysiology is still in debate. Considering that reactive astrogliosis is a common finding in brain of GA I patients, in the present study we investigated the effects of GA and 3OHGA on glial activity determined by S100B release by rat C6-glioma cells. We also evaluated the effects of these organic acids on some parameters of oxidative stress in these astroglial cells. We observed that GA and 3OHGA significantly increased S100B secretion and thiobarbituric acid-reactive substances (lipid peroxidation), whereas GA markedly decreased reduced glutathione levels in these glioma cells. This is the first report demonstrating that the major metabolites accumulating in GA I activate S100B secretion in astroglial cells, indicating activation of these cells. We also showed that GA and 3OHGA induced oxidative stress in C6 lineage cells, confirming previous findings observed in brain fresh tissue. It is therefore presumed that reactive glial cells and oxidative damage may underlie at least in part the neuropathology of GA I.
Authors:
André Quincozes-Santos; Rafael Borba Rosa; Guilhian Leipnitz; Daniela Fraga de Souza; Bianca Seminotti; Moacir Wajner; Carlos Alberto Gonçalves
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-01
Journal Detail:
Title:  Metabolic brain disease     Volume:  25     ISSN:  1573-7365     ISO Abbreviation:  Metab Brain Dis     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-04     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8610370     Medline TA:  Metab Brain Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-8     Citation Subset:  IM    
Affiliation:
Departamento de Bioquímica, Universidade Federal de Rio Grande do Sul, Porto Alegre, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Metabolism, Inborn Errors / enzymology,  metabolism*,  pathology
Animals
Astrocytes / metabolism,  pathology,  secretion*
Atrophy
Brain Diseases, Metabolic / enzymology,  metabolism*,  pathology
Cell Line, Tumor
Corpus Striatum / enzymology,  metabolism,  pathology
Gliosis / enzymology,  metabolism,  pathology
Glutarates / metabolism*,  pharmacology
Glutaryl-CoA Dehydrogenase / deficiency*
Glutathione / antagonists & inhibitors
Lipid Peroxidation / drug effects,  physiology
Nerve Growth Factors / metabolism,  secretion*
Oxidative Stress / drug effects,  physiology
Rats
S100 Proteins / metabolism,  secretion*
Thiobarbituric Acid Reactive Substances / metabolism
Chemical
Reg. No./Substance:
0/3-hydroxyglutaric acid; 0/Glutarates; 0/Nerve Growth Factors; 0/S-100 calcium-binding protein beta subunit; 0/S100 Proteins; 0/Thiobarbituric Acid Reactive Substances; 110-94-1/glutaric acid; 70-18-8/Glutathione; EC 1.3.99.7/Glutaryl-CoA Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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