Superoxide generated by lysophosphatidylcholine induces endothelial nitric oxide synthase downregulation in human endothelial cells

Shinkyu Choi, Seonghee Park, Guo Hua Liang, Ji Aee Kim, Suk Hyo Suh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We examined the mechanism through which lysophosphatidylcholine (LPC) induces endothelial nitric oxide (eNOS) downregulation. Human umbilical vein endothelial cells (HUVECs) were treated with LPC (50-150 μM) for 0.5-2 h or the reactive oxygen species (ROS) donors, xanthine/xanthine oxidase (X/XO), 1,4-hydroquinone (HQ) or tert-butylhydroperoxide (TBHP) for 2 h. Protein levels of eNOS, superoxide dismutase1 (SOD1), catalase, and phospho-extracellular signal regulated kinase 1/2 (pERK 1/2) were assessed using immunoblotting. LPC treatment reduced SOD1 levels but increased catalase levels. The superoxide donors X/XO and HQ showed similar effects. The hydroperoxide donor TBHP increased SOD1 levels but did not change catalase levels. LPC concentration-and time-dependently decreased eNOS levels, but this effect was blocked by antioxidants and SOD and potentiated by the SOD1 inhibitor, ammonium tetrathiomolybdate. LPC and X/XO inhibited ERK1/2 phosphorylation, whereas TBHP stimulated phosphorylation. Taken together, these data indicate that LPC induces superoxide overload in HUVECs via SOD1 inhibition and downregulates phospho-ERK1/2 and eNOS levels.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalCellular Physiology and Biochemistry
Volume25
Issue number2-3
DOIs
StatePublished - 2010

Keywords

  • Endothelial cell
  • ENOS
  • Lysophosphatidylcholine
  • Superoxide
  • Vascular dysfunction

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