Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase

Mahsa Rouhanizadeh, Juliana Hwang, Roza E. Clempus, Laura Marcu, Bernard Lassègue, Alex Sevanian, Tzung K. Hsiai

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Modified low-density lipoprotein (LDL) induces reactive oxygen species (ROS) production by vascular cells. It is unknown if specific oxidized components in these LDL particles such as oxidized-1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine (ox-PAPC) can stimulate ROS production. Bovine aortic endothelial cells (BAEC) were incubated with ox-PAPC (50 μg/ml). At 4 h, ox-PAPC significantly enhanced the rate of O2 -. production. Pretreatment of BAEC in glucose-free Dulbecco's modified Eagle's medium plus 10 mM 2-deoxyglucose (2-DOG), the latter being an antimetabolite that blocks NADPH production by the pentose shunt, significantly reduced the rate of O2 -. production. The intensity of NAD(P)H autofluorescence decreased by 28 ± 12% in BAEC incubated with ox-PAPC compared to untreated cells, with a further decrease in the presence of 2-DOG. Ox-PAPC also increased Nox4 mRNA expression by 2.4-fold ± 0.1 while pretreatment of BAEC with the small interfering RNA (siNox4) attenuated Nox4 RNA expression. Ox-PAPC further reduced the level of glutathione while pretreatment with apocynin (100 μM) restored the GSH level (control = 22.54 ± 0.23, GSH = 18.06 ± 0.98, apocynin = 22.55 ± 0.60, ox-PAPC + apocynin = 21.17 ± 0.36 nmol/106 cells). Treatment with ox-PAPC also increased MMP-2 mRNA expression accompanied by a 1.5-fold increase in MMP-2 activity. Ox-PAPC induced vascular endothelial O2- . production that appears to be mediated largely by NADPH oxidase activity.

Original languageEnglish (US)
Pages (from-to)1512-1522
Number of pages11
JournalFree Radical Biology and Medicine
Volume39
Issue number11
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

Keywords

  • Matrix metalloproteinases (MMPs)
  • NAD(P)H oxidase
  • Ox-PAPC
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase'. Together they form a unique fingerprint.

  • Cite this