Inhibition effect of arachidonic acid on hypoxia-induced [Ca(2+)](i) elevation in PC12 cells and human pulmonary artery smooth muscle cells.
Respir Physiol Neurobiol
; 162(1): 18-23, 2008 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-18455484
ABSTRACT
[Ca(2+)](i) elevation is a key event when O(2) sensitive cells, e.g. PC12 cells and pulmonary artery smooth muscle cells, face hypoxia. Ca(2+) entry pathways in mediating hypoxia-induced [Ca(2+)](i) elevation include voltage-gated Ca(2+) channels (VGCCs), transient receptor potential (TRP) channel and Na(+)-Ca(2+) ex-changer (NCX). In the pulmonary artery, accumulated evidence strongly suggests that prostaglandins (PGs) are involved in pulmonary inflammation and cause vasoconstriction during hypoxia. In this study, we investigated the effect of arachidonic acid (AA), the upstream substrate for PGs, on hypoxia response in O(2) sensitive cells. Exogenous application of AA significantly inhibited hypoxia-induced [Ca(2+)](i) elevation. This effect was due to AA itself rather than its degenerative products. The pharmacological modulation of endogenous AA showed that the prevention of AA generation by blockage of cPLA2, diacylglycerol (DAG) lipase and fatty acid hydrolysis (FAAH), augments hypoxia-induced [Ca(2+)](i) elevation, whereas prevention of AA degeneration attenuates hypoxia-induced [Ca(2+)](i) elevation. Over-expression of COX2 enhances hypoxia-induced [Ca(2+)](i) elevation and this enhancement is reversed by exogenous AA. Our results suggest that AA inhibits hypoxia response. The dynamic alterations in cellular lipids might determine cell response to hypoxia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
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Cálcio
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Células PC12
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Ácido Araquidônico
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Miócitos de Músculo Liso
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Hipóxia
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article