| Catecholamine-induced oligodendrocyte cell death in culture is developmentally regulated and involves free radical generation and differential activation of caspase-3. | |
| | |
MedLine Citation:
|
PMID: 12420309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oligodendrocyte cultures were used to study the toxic effects of catecholamines. Our results showed that catecholamine-induced toxicity was dependent on the dose of dopamine or norepinephrine used and on the developmental stage of the cultures, with oligodendrocyte progenitors being more vulnerable. A role for oxidative stress and apoptosis on the mechanism of action of catecholamines on oligodendrocyte cell death was next assessed. Catecholamines caused a reduction in intracellular glutathione levels, an accumulation in reactive oxygen species and in heme oxygenase-1, the 32 kDa stress-induced protein. All these changes were prevented by N-acetyl-L-cysteine, a thiocompound with antioxidant activity and a precursor of glutathione, and were more pronounced in progenitors than mature cells, which could contribute to their higher susceptibility. Apoptotic cell death, as assessed by activation of caspase-9 and -3 and cleavage of poly(ADP-ribose) polymerase (a substrate of caspase-3), was only observed in oligodendrocyte progenitors. Pretreatment with zVAD, a general caspase inhibitor, prevented activation of caspase-9 and -3, DNA fragmentation, and decreased progenitors cell death. Furthermore, the expression levels of procaspase-3 and the ratio of the proapoptotic protein bax to antiapoptotic protein bcl-xl were several folds higher in immature than mature oligodendrocytes. Taken together, these results strongly suggest that the catecholamine-induced cytotoxicity in oligodendrocytes is developmentally regulated, mediated by oxidative stress, and have characteristics of apoptosis in progenitor cells. |
| | |
Authors:
|
Amani Khorchid; Gabriela Fragoso; Gordon Shore; Guillermina Almazan |
Related Documents
:
|
15911099 - Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia... 11877339 - Kainic acid-induced neuronal cell death in cerebellar granule cells is not prevented by... 19956899 - Apoptosis induction of human leukemia cells by streptomyces sp. sy-103 metabolites thro... 10753639 - Resistance to apoptosis is correlated with the reduced caspase-3 activation and enhance... 14705839 - Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. 7568069 - Studies of the lamin proteinase reveal multiple parallel biochemical pathways during ap... 15021969 - Functional interactions between mucosal il-1, il-ra and tgf-beta 1 in ulcerative colitis. 15826379 - Evolution and integration of innate immune recognition systems: the toll-like receptors. 15361359 - Effects of dexamethasone on muc5ac mucin production by primary airway goblet cells. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Glia Volume: 40 ISSN: 0894-1491 ISO Abbreviation: Glia Publication Date: 2002 Dec |
Date Detail:
|
Created Date: 2002-11-06 Completed Date: 2003-08-01 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
|
Languages: eng Pagination: 283-99 Citation Subset: IM |
Copyright Information:
|
Copyright 2002 Wiley-Liss, Inc. |
Affiliation:
|
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcysteine
/
metabolism,
pharmacology Animals Animals, Newborn Apoptosis / drug effects, physiology* Asphyxia Neonatorum / enzymology, physiopathology Brain / enzymology, growth & development*, physiopathology Caspase 3 Caspases / metabolism Catecholamines / metabolism, toxicity* Cell Differentiation / drug effects, physiology* Cells, Cultured Enzyme Inhibitors / pharmacology Free Radicals / metabolism Genes, bcl-2 / genetics Glutathione / metabolism Heme Oxygenase (Decyclizing) / metabolism Heme Oxygenase-1 Humans Infant, Newborn Leukomalacia, Periventricular / enzymology, etiology, physiopathology Membrane Proteins Oligodendroglia / drug effects, enzymology* Oxidative Stress / drug effects, physiology* Poly(ADP-ribose) Polymerases / metabolism Rats Rats, Sprague-Dawley Stem Cells / drug effects, enzymology* |
| Chemical | |
Reg. No./Substance:
|
0/Catecholamines; 0/Enzyme Inhibitors; 0/Free Radicals; 0/Membrane Proteins; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; EC 1.14.99.3/HMOX1 protein, human; EC 1.14.99.3/Heme Oxygenase (Decyclizing); EC 1.14.99.3/Heme Oxygenase-1; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; 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
Previous Document: Activation of PP2A-like phosphatase and modulation of tau phosphorylation accompany stress-induced a...
Next Document: Trafficking of PLP/DM20 and cAMP signaling in immortalized jimpy oligodendrocytes.