Document Detail


Cystamine inhibits transglutaminase and caspase-3 cleavage in glutamate-exposed astroglial cells.
MedLine Citation:
PMID:  13130505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the precise role of transglutaminase in cell death is unknown, several findings demonstrate that tissue transglutaminase selectively accumulates in cells undergoing apoptosis both in vivo and in vitro. Calcium-dependent transglutaminase reactions are also implicated in several neurodegenerative diseases, including alterations in the release of excitatory amino acids. One prevalent theme in cell damage induced by excitotoxic stimuli in different regions of the CNS is that apoptosis may be executed by intracellular caspase proteases. Furthermore, the presence of functional ion channel-gated receptors in glial cells suggests that also astrocytes can be susceptible to glutamate's toxic effects. In this study, we demonstrated that prolonged exposure to glutamate (100 microM) of cultured astrocytes caused an increase in the expression of tissue transglutaminase (tTG). This effect was prevented by preincubation with GYKI 52466, an antagonist of AMPA/KA receptors. Glutamate exposure also promoted an increase in caspase-3 compared with control cultures. Confocal laser microscopy analysis demonstrated the presence of activated caspase-3 in the cytoplasm as well as in the nucleus. The inhibition of TG-catalyzed reactions by cystamine (1 mM) blocked the activation pathway of caspase-3, with an evident reduction of enzyme cleavage. These results suggest that glutamate increased both TG and caspase-3 in astroglial cells early in the excitotoxin-induced events.
Authors:
R Ientile; A Campisi; G Raciti; D Caccamo; M Currò; G Cannavò; G Li Volti; S Macaione; A Vanella
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  74     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-17     Completed Date:  2003-11-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  52-9     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Department of Biochemical, Physiological, and Nutritional Sciences, University of Messina, Messina, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / drug effects*,  enzymology
Caspase 3
Caspases / antagonists & inhibitors*,  metabolism
Cells, Cultured
Cerebral Cortex / drug effects*,  enzymology
Cystamine / pharmacology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Glutamic Acid / pharmacology*
Rats
Rats, Wistar
Transglutaminases / antagonists & inhibitors*,  metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 51-85-4/Cystamine; 56-86-0/Glutamic Acid; EC 2.3.2.13/Transglutaminases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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


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