| Cystamine inhibits transglutaminase and caspase-3 cleavage in glutamate-exposed astroglial cells. | |
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MedLine Citation:
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PMID: 13130505 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Journal of neuroscience research Volume: 74 ISSN: 0360-4012 ISO Abbreviation: J. Neurosci. Res. Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-09-17 Completed Date: 2003-11-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: United States |
Other Details:
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Languages: eng Pagination: 52-9 Citation Subset: IM |
Copyright Information:
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Copyright 2003 Wiley-Liss, Inc. |
Affiliation:
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Department of Biochemical, Physiological, and Nutritional Sciences, University of Messina, Messina, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
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