Inhibition effect of arachidonic acid on hypoxia-induced [Ca2+ ] i elevation in PC12 cells and human pulmonary artery smooth muscle cells

• Published in: Respiratory physiology & neurobiology Vol. 162; no. 1; pp. 18 - 23
• Main Authors: Meng, Fei, To, Wilson King Lim, Gu, Yuchun
• Format: Journal Article
• Language: English
• Published: Amsterdarm Elsevier B.V 2008; Elsevier
• Subjects: Arachidonic acid; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Human pulmonary artery smooth muscle cell; Hypoxia; Intracellular Ca 2; Medical Education; PC12; Pulmonary/Respiratory; Vertebrates: respiratory system; PC12; Hypoxia; Human pulmonary artery smooth muscle cell; Arachidonic acid; Intracellular Ca 2; Human; Oxygen; Calcium; Smooth muscle; Inorganic element; Respiratory system; In vitro; Pulmonary artery; Vertebrata; Cell line; Mammalia; Neuron; Pulmonary vessel; Blood vessel; Circulatory system; Inhibition; Intracellular; Intracellular Ca2
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2008.03.007

Abstract [Ca2+ ] i elevation is a key event when O2 sensitive cells, e.g. PC12 cells and pulmonary artery smooth muscle cells, face hypoxia. Ca2+ entry pathways in mediating hypoxia-induced [Ca2+ ] i elevation include: voltage-gated Ca2+ channels (VGCCs), transient receptor potential (TRP) channel and Na+ –Ca2+ 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 O2 sensitive cells. Exogenous application of AA significantly inhibited hypoxia-induced [Ca2+ ] 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 [Ca2+ ] i elevation, whereas prevention of AA degeneration attenuates hypoxia-induced [Ca2+ ] i elevation. Over-expression of COX2 enhances hypoxia-induced [Ca2+ ] 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.