Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells

Author:

Raman Puneet1,Madhavpeddi Lakshmi1,Gonzales Rayna J.1

Affiliation:

1. Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, Phoenix, Arizona

Abstract

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 E2 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.

Funder

Valley Reserach Partnership

Sarver Heart Center Mentored Medical Student Award

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3