Journal article
Differential effects of ethanol on the expression of cyclo-oxygenase in cultured cortical astrocytes and neurons
Journal of neurochemistry, Vol.76(5), pp.1354-1363
2001
DOI: 10.1046/j.1471-4159.2001.00129.x
PMID: 11238720
Abstract
The developing central nervous system is a primary target of ethanol toxicity. The teratogenic effect of ethanol may result from its action on prostaglandins. Prostaglandins are generated through the release of arachidonic acid (AA) by the action of cytosolic phospholipase A(2) (cPLA(2)) on membrane-bound phospholipids and the catalytic conversion of AA to prostaglandin E(2) (PGE(2)) by cyclo-oxygenase (COX). COX is expressed in two isoforms, constitutive COX1 and inducible COX2. Cultured astrocytes and neurons from immature cerebral cortex were used as in vitro models to investigate the effect of ethanol on PGE(2) synthesis. In both cell types, neither the activity nor the expression of cPLA(2) was affected by ethanol. PGE(2) was synthesized by astrocytes and neurons. Ethanol (200-400 mg/dL for 24 h) significantly increased PGE(2) production in both cell types and the ethanol-induced increase in PGE(2) accumulation in astrocytes was significantly greater than in neurons. These increases resulted from the effects of ethanol on COX. Overall COX activity was up-regulated by ethanol in astrocytes and neurons, and indomethacin, a nonselective blocker for COX, eliminated the ethanol-induced increases of COX activity in both cell types. Increased COX activity in astrocytes resulted from an increase in COX2 expression. NS-398, a selective COX2 blocker, completely inhibited ethanol-induced alterations in COX activity. In neurons, however, ethanol had a direct effect on COX activity in the absence of a change in COX expression. NS-398 only partially blocked ethanol-induced increases in neuronal COX activity. Thus, astrocytes are a primary target of ethanol and ethanol-induced increases in glial PGE(2) synthesis are mediated by COX, principally COX2. Ethanol toxicity may be mediated through PGE(2) in immature cortical cells.
Details
- Title: Subtitle
- Differential effects of ethanol on the expression of cyclo-oxygenase in cultured cortical astrocytes and neurons
- Creators
- JIA Luo - University of IowaChristine L. B Lindström - University of IowaArthur Donahue - University of IowaMichael W Miller - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of neurochemistry, Vol.76(5), pp.1354-1363
- DOI
- 10.1046/j.1471-4159.2001.00129.x
- PMID
- 11238720
- NLM abbreviation
- J Neurochem
- ISSN
- 0022-3042
- eISSN
- 1471-4159
- Publisher
- Blackwell
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology
- Record Identifier
- 9984186550302771
Metrics
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