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

Puneet Raman, Lakshmi Madhavpeddi, Rayna J Gonzales

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)C545-C553
JournalAmerican journal of physiology. Cell physiology
Volume314
Issue number5
DOIs
StatePublished - May 1 2018
Externally publishedYes

Keywords

  • cyclooxygenase-2
  • glycosylation
  • inflammation
  • palmitate, vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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