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

Abstract

Although low concentrations (10 microg/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 (beta 1-->4) galactosyltransferase (GalT-2) and produce lactosyceramide (LacCer). LacCer, in turn, generated superoxide radicals (O(2)(.-)). This is accompanied by the phosphorylation/activation of a cytosolic transcriptional factor p(44) 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, O(2)(.-)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.

• Authors: Subroto Chatterjee, Judith A Berliner, Ganesamoorthy G Subbanagounder, Anil K Bhunia, Steve Koh
• Journal: Glycoconjugate journal (Glycoconj J) Vol. 20 Issue 5 Pg. 331-8 ( 2004) ISSN: 0282-0080 [Print] United States
• PMID: 15229397 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol
• Lipoproteins, LDL
• Morpholines
• Phospholipid Ethers
• Phospholipids
• Plant Proteins
• Sphingolipids
• oxidized low density lipoprotein
• Superoxides
• Galactosyltransferases
• galactosylxylosylprotein 3-beta-galactosyltransferase
• MMK4 protein, Medicago sativa
• Mitogen-Activated Protein Kinases

Topics

• Aorta (cytology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Galactosyltransferases (antagonists & inhibitors, metabolism)
• Humans
• Lipoproteins, LDL (chemistry, pharmacology)
• Mitogen-Activated Protein Kinases (metabolism)
• Morpholines (pharmacology)
• Myocytes, Smooth Muscle (cytology, drug effects, enzymology, metabolism)
• Oxidation-Reduction
• Phospholipid Ethers (pharmacology)
• Phospholipids (pharmacology)
• Plant Proteins
• Sphingolipids (pharmacology)
• Superoxides (metabolism)