Cholesterol-3-beta, 5-alpha, 6-beta-triol induced PI3K-Akt-eNOS-dependent cyclooxygenase-2 expression in endothelial cells

Po Lin Liao, Yu Wen Cheng, Ching Hao Li, Yi Ling Lo, Jaw Jou Kang

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Oxidized cholesterols belong to a subgroup of oxLDLs which play major roles in atherosclerosis. In order to investigate the contribution of oxysterols from oxLDLs in atherosclerosis, cholesterol-3-beta, 5-alpha, 6-beta-triol (α-Triol) was studied in human umbilical vein endothelial cells. We found that α-Triol concentration- and time-dependently enhanced COX-2 protein expression and mRNA production followed by PGE2 generation in human umbilical vein endothelial cells. In addition, α-Triol upregulated peNOS1177 protein phosphorylation and concentration-dependently increased nitric oxide production. eNOS1177 phosphorylation was abrogated by the PI3K inhibitor, LY294002. In studying the mechanisms involved in α-Triol-induced COX-2/PGE2 production, inhibitors of NOS, PI3K, p38, and NF-κB, effectively attenuated COX-2 protein induction and mRNA expression, suggesting that the PI3K-Akt-eNOS pathway, p38MAPK, and NF-κB are involved in α-Triol-induced COX-2 expression, and following increases in p38 and Akt phosphorylation, the concentration-dependent inhibition of COX-2 protein expression by L-NAME further suggested their involvement at the translation level. We concluded that α-Triol increases COX-2 mRNA and protein expression via coordination with the PI3K-Akt-eNOS pathway and NF-κB. Moreover, COX-2 gene expression might be regulated by activated p38 MAPK in another unknown regulation pathway. Our findings also suggested that α-Triol might contribute to the effect of induced atherosclerosis in humans through COX-2 production in endothelial cells.

Original languageEnglish
Pages (from-to)172-178
Number of pages7
JournalToxicology Letters
Volume190
Issue number2
DOIs
Publication statusPublished - Oct 28 2009
Externally publishedYes

Keywords

  • Atherosclerosis
  • Cholesterol-3-beta, 5-alpha, 6-beta-triol
  • Cyclooxygenase-2
  • Nitric oxide

ASJC Scopus subject areas

  • Toxicology

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