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

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

Author Gloria, Maria Aparecida da Autor UNIFESP Google Scholar
Cenedeze, Marcos Antonio Autor UNIFESP Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Camara, Niels Olsen Saraiva Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract 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 mmIIg). 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 mu M) decreased COX-2, HO-1, hypoxiainducible factor-1 alpha 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.
Keywords endothelial cell
hypoxia
indomethacin
cyclooxygenase
heme oxygenase 1
Language English
Date 2006-09-01
Published in Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 39, n. 9, p. 1189-1196, 2006.
ISSN 0100-879X (Sherpa/Romeo, impact factor)
Publisher Assoc Bras Divulg Cientifica
Extent 1189-1196
Origin http://dx.doi.org/10.1590/S0100-879X2006000900006
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000240545900006
SciELO ID S0100-879X2006000900006 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/29119

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