The blockade of cyclooxygenases-1 and -2 reduces the effects of hypoxia on endothelial cells

Autor(es)

M.A. Gloria ^[1] ; M.A. Cenedeze ^[2] ; A. Pacheco-Silva ^[3] ; N.O.S. Câmara

Afiliação do(s) autor(es)

^[1] Fundação Oswaldo Ramos. do Rim e Hipertensão. Universidade Federal de São Paulo - Brasil

^[2] Fundação Oswaldo Ramos. do Rim e Hipertensão. Universidade Federal de São Paulo - Brasil

^[3] Fundação Oswaldo Ramos. do Rim e Hipertensão. Universidade Federal de São Paulo - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 39, n. 9, p. 1189-1196, 2006-09-00.

Resumo

Hypoxia activates endothelial cells by the action of reactive oxygen species generated in part by cyclooxygenases (COX) production enhancing leukocyte transmigration. We investigated the effect of specific COX inhibition on the function of endothelial cells exposed to hypoxia. Mouse immortalized endothelial cells were subjected to 30 min of oxygen deprivation by gas exchange. Acridine orange/ethidium bromide dyes and lactate dehydrogenase activity were used to monitor cell viability. The mRNA of COX-1 and -2 was amplified and semi-quantified before and after hypoxia in cells treated or not with indomethacin, a non-selective COX inhibitor. Expression of RANTES (regulated upon activation, normal T cell expressed and secreted) protein and the protective role of heme oxygenase-1 (HO-1) were also investigated by PCR. Gas exchange decreased partial oxygen pressure (PaO2) by 45.12 ± 5.85% (from 162 ± 10 to 73 ± 7.4 mmHg). Thirty minutes of hypoxia decreased cell viability and enhanced lactate dehydrogenase levels compared to control (73.1 ± 2.7 vs 91.2 ± 0.9%, P < 0.02; 35.96 ± 11.64 vs 22.19 ± 9.65%, P = 0.002, respectively). COX-2 and HO-1 mRNA were up-regulated after hypoxia. Indomethacin (300 µM) decreased COX-2, HO-1, hypoxia-inducible factor-1alpha and RANTES mRNA and increased cell viability after hypoxia. We conclude that blockade of COX up-regulation can ameliorate endothelial injury, resulting in reduced production of chemokines. (AU)

• Processo FAPESP: 04/13826-5 - Contribuição ao aumento da sobrevida do enxerto em transplante de rim: papel dos mecanismos imunológicos e não imunológicos na fisiopatogenia da insuficiência renal aguda
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/08311-6 - Mecanismos moleculares, celulares e fisiopatológicos da insuficiência renal aguda
• Beneficiário: Nestor Schor
• Modalidade de apoio: Auxílio à Pesquisa - Temático