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Double-label expression studies of prostacyclin synthase, thromboxane synthase and COX isoforms in normal aortic endothelium.
Kawka, Douglas W; Ouellet, Marc; Hétu, Pierre-Olivier; Singer, Irwin I; Riendeau, Denis.
Afiliación
  • Kawka DW; Departments of Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Biochim Biophys Acta ; 1771(1): 45-54, 2007 Jan.
Article en En | MEDLINE | ID: mdl-17189713
We have performed double-label immunofluorescence microscopy studies to evaluate the extent of co-localization of prostacyclin synthase (PGIS) and thromboxane synthase (TXS) with cyclooxygenase (COX)-1 and COX-2 in normal aortic endothelium. In dogs, COX-2 expression was found to be restricted to small foci of endothelial cells while COX-1, PGIS and TXS were widely distributed throughout the endothelium. Quantification of the total cross-sectioned aortic endothelium revealed a 6- to 7-fold greater expression of COX-1 relative to COX-2 (55 vs. 8%) and greater co-distribution of PGIS with COX-1 compared to COX-2 (19 vs. 3%). These results are in contrast to the extensive co-localization of PGIS and COX-2 in bronchiolar epithelium. In rat and human aortas, immunofluorescence studies also showed significant COX-1 and PGIS co-localization in the endothelium. Only minor focal COX-2 expression was detected in rat endothelium, similar to the dog, while COX-2 was not detected in human specimens. Inhibition studies in rats showed that selective COX-1 inhibition caused a marked reduction of 6-keto-PGF(1alpha) and TXB(2) aortic tissue levels, while COX-2 inhibition had no significant effect, providing further evidence for a functionally larger contribution of COX-1 to the synthesis of prostacyclin and thromboxane in aortic tissue. The data suggest a major role for COX-1 in the production of both prostacyclin and thromboxane in normal aortic tissue. The extensive co-localization of PGIS and COX-2 in the lung also indicates significant tissue differences in the co-expression patterns of these two enzymes.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Tromboxano-A Sintasa / Endotelio Vascular / Regulación Enzimológica de la Expresión Génica / Prostaglandina-Endoperóxido Sintasas / Oxidorreductasas Intramoleculares / Sistema Enzimático del Citocromo P-450 Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Tromboxano-A Sintasa / Endotelio Vascular / Regulación Enzimológica de la Expresión Génica / Prostaglandina-Endoperóxido Sintasas / Oxidorreductasas Intramoleculares / Sistema Enzimático del Citocromo P-450 Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos