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Titolo:
The effect of hypoxia on endogenous corneal epithelial eicosanoids
Autore:
Mieyal, PA; Bonazzi, A; Jiang, HL; Dunn, MW; Schwartzman, ML;
Indirizzi:
New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 Pharmacol, Valhalla, NY 10595 USA
Titolo Testata:
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
fascicolo: 8, volume: 41, anno: 2000,
pagine: 2170 - 2176
SICI:
0146-0404(200007)41:8<2170:TEOHOE>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
RABBIT CORNEA; ENDOTHELIAL-CELLS; 12(S)-HYDROXYEICOSATETRAENOIC ACID; 12(R)-HYDROXYEICOSATRIENOIC ACID; INFLAMMATORY EICOSANOIDS; ARACHIDONIC-ACID; METABOLISM; OXYGEN; STIMULATION; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Schwartzman, ML New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 lla, NY 10595 USA
Citazione:
P.A. Mieyal et al., "The effect of hypoxia on endogenous corneal epithelial eicosanoids", INV OPHTH V, 41(8), 2000, pp. 2170-2176

Abstract

PURPOSE. Injury to the corneal epithelium increases arachidonic acid (AA) metabolism through the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 pathways. The authors used the rabbit corneal organ culture modelto demonstrate the effect of hypoxia on the endogenous formation of 12-hydroxy-5,8,11,14-eicosatetraenoic acid (12-HETE), 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE), and prostaglandin (PG) E-2 by the intact cornea in the absence of exogenously added cofactors or substrate. METHODS. Rabbit corneas were isolated and cultured for 24 hours in normoxia or hypoxia. After culture, PGE, in media was quantitated by enzyme immunoassay. 12-HETE and 12-HETrE were extracted from culture media and corneal epithelium and quantitated by negative chemical ionization-gas chromatography-mass spectrometry. COX-1 and -2 protein expression in corneal epithelium was determined by Western blot. Acute (2 hours) COX activity in normoxia and hypnoxia was determined as the conversion rate of [C-14]AA to [C-14]PGE(2), quantitated through reverse-phase-high-performance liquid chromatographyand radiodetection. RESULTS. In the media of cultured rabbit corneas, both 12-HETE and 12-NETrE were detected, with 12-HETrE levels being four times higher. Hypoxia did not significantly increase extracellular 12-HETE or 12-HETrE; however, it caused more than 90% inhibition of PGE, synthesis. Intracellular 12-HETE and12-HETrE were undetectable in normal corneas but increased to 7.7 +/- 1.3 and 2.2 +/- 0.4 ng/mg protein, respectively, after 24 hours in culture. Culture in hypoxia further increased intracellular 12-HETE threefold but had no additional effect on 12-HETrE. CONCLUSIONS. Hypoxia creates an environment in which epithelial COX activity is severely suppressed, whereas cytochrome P450-AA and/or 12-LOX metabolizing activity is maintained or enhanced. Additionally, the findings suggest that 12-HETE produced by the corneal epithelium acts intracellularly to promote corneal edema, whereas 12-HETrE acts in a paracrine manner to initiate an inflammatory cascade that can elicit neutrophil chemotaxis and neovascularization of the cornea.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 01:00:45