Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation

Subroto Chatterjee, Judith A. Berliner, Ganesamoorthy G. Subbanagounder, Anil K. Bhunia, Steve Koh

Research output: Contribution to journalArticle

Abstract

Although low concentrations (10 μg/ml) of oxidized LDL density lipoproteins (Ox-LDL) and minimally modified LDL (MM-LDL) can stimulate the proliferation of aortic smooth muscle cells the biologically active component responsible for this phenomena has not been identified. Here we report that the 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-4-phosphocholine (m/e594.3) (POVPC) present in MM-LDL but not 1-palmitoyl-2-glutaryl-sn-glycero-3-phophochline (m/e610.2)(PGPC) can stimulate the activity of UDP-galactose:glucosylceramide (β 1→4) galactosyltransferase (GalT-2) and produce lactosyceramide (LacCer). LacCer, in turn, generated superoxide radicals (O2 .-). This is accompanied by the phosphorylation/activation of a cytosolic transcriptional factor p44 MAPK and the subsequent proliferation of human aortic smooth muscle cells. D-threo-1-phenyl-2- decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of GalT-2, impaired the induction of GalT-2 activity, O2.- generation, and cell proliferation. Thus POVPC may serve as a surrogate in MM-LDL mediated induction of aortic smooth muscle cells (A-SMC) proliferation via GalT-2 activation. The LacCer produced as a consequence of GalT-2 activation may serve as a lipid second messenger in the activation of an oxidant sensitive transcriptional pahtway that ultimately leads to cell proliferation and may contribute to the pathophysiology of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalGlycoconjugate Journal
Volume20
Issue number5
DOIs
StatePublished - Dec 1 2003

Keywords

  • Galactosyltransferase
  • Minimally modified low density lipoproteins
  • Oxidized phospholipids
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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