环氧合酶
血管平滑肌
炎症
前列腺素
内分泌学
内科学
促炎细胞因子
二十烷酸
化学
前列腺素
生物
生物化学
花生四烯酸
医学
酶
平滑肌
作者
Puneet Raman,Lakshmi Madhavpeddi,Rayna J. Gonzales
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2018-01-31
卷期号:314 (5): C545-C553
被引量:10
标识
DOI:10.1152/ajpcell.00254.2017
摘要
Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia. During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events. Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators. However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated. We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells. Cells were treated with palmitate, COX-2 protein levels were assessed using Western analysis, and activity was assessed via ELISA. We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band). This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2. Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E 2 production that was also attenuated by a glycosylation inhibitor. Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition. Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle. It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
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