Unsaturated free fatty acids inhibit Ca(2+) mobilization and NO release in endothelial cells
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概要
- 論文の詳細を見る
Circulating free fatty acids (FFAs) are elevated in various disorders like states ofinsulin resistance, and an increase of FFAs has been reported to be associated withendothelial dysfunction. To investigate the effect of FFAs on vascular endothelial cells,we measured nitric oxide (NO) release and intracellular free calcium concentration([Ca2+]i ) in cultured bovine aortic endothelial cells (BAECs). Monounsaturated FFAssuch as oleic acid (OA) and polyunsaturated FFAs such as linoleic acid (LA)dose-dependently (10-100 µmol/L) inhibited NO release from BAECs stimulated byadenosine 5-(3-O-thio)triphosphate (ATPγS) whereas saturated FFAs such as palmiticacid had no effect on NO release. ATPγS induced a biphasic increase in [Ca2+]i, whichconsisted of a rapid increase followed by a sustained increase. OA and LA inhibitedATPγS-induced Ca2+ release from intracellular Ca2+ stores and increase in Ca2+influx from extracellular space. In addition, OA and LA rapidly decreased sustainedincrease in [Ca2+]i induced by ATPγS when OA or LA was added after stimulationwith ATPγS. Impaired Ca2+ mobilization by unsaturated FFAs (UFFAs) wascompletely reversed by treatment with bovine serum albumin (1 mg/ml) indicating thatinhibitory effect of FFAs was not caused by cytotoxic effect. In spite of this inhibitoryeffect of UFFAs, neither OA nor LA had any effect on phosphoinositide hydrolysisevoked by ATPγS. From these results, elevated UFFA may contribute to impaired NOproduction through inhibition of receptor-mediated Ca2+ mobilization and Ca2+ influxin pathological conditions such as multiple risk factor syndrome and insulin resistance.
- 神戸大学の論文
著者
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Yokoyama Mitsuhiro
神戸大学医学部
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Kawashima Seinosuke
神戸大学医学系研究科
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Hirata Ken-ichi
Department Cardiology Kobe University Graduate School Of Medicine
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Kuroda Ryohei
神戸大学医学系研究科
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Hirata Ken-ichi
神戸大学医学系研究科
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