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

Subroto B 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 - 2003

Fingerprint

Cell proliferation
Smooth Muscle Myocytes
Muscle
Cell Proliferation
Chemical activation
LDL Lipoproteins
Cells
Uridine Diphosphate Galactose
Glucosylceramides
Galactosyltransferases
Phosphorylation
Phosphorylcholine
Mitogen-Activated Protein Kinase 3
Second Messenger Systems
Oxidants
Superoxides
Lipoproteins
Atherosclerosis
glucosylceramide beta-1-4-galactosyltransferase
oxidized low density lipoprotein

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation. / Chatterjee, Subroto B; Berliner, Judith A.; Subbanagounder, Ganesamoorthy G.; Bhunia, Anil K.; Koh, Steve.

In: Glycoconjugate Journal, Vol. 20, No. 5, 2003, p. 331-338.

Research output: Contribution to journalArticle

@article{b914f76fe878403f92e610da3b51b927,
title = "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 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.",
keywords = "Galactosyltransferase, Minimally modified low density lipoproteins, Oxidized phospholipids, Proliferation",
author = "Chatterjee, {Subroto B} and Berliner, {Judith A.} and Subbanagounder, {Ganesamoorthy G.} and Bhunia, {Anil K.} and Steve Koh",
year = "2003",
doi = "10.1023/B:GLYC.0000033629.54962.68",
language = "English (US)",
volume = "20",
pages = "331--338",
journal = "Glycoconjugate Journal",
issn = "0282-0080",
publisher = "Springer Netherlands",
number = "5",

}

TY - JOUR

T1 - Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation

AU - Chatterjee, Subroto B

AU - Berliner, Judith A.

AU - Subbanagounder, Ganesamoorthy G.

AU - Bhunia, Anil K.

AU - Koh, Steve

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - Galactosyltransferase

KW - Minimally modified low density lipoproteins

KW - Oxidized phospholipids

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=3543099692&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3543099692&partnerID=8YFLogxK

U2 - 10.1023/B:GLYC.0000033629.54962.68

DO - 10.1023/B:GLYC.0000033629.54962.68

M3 - Article

C2 - 15229397

AN - SCOPUS:3543099692

VL - 20

SP - 331

EP - 338

JO - Glycoconjugate Journal

JF - Glycoconjugate Journal

SN - 0282-0080

IS - 5

ER -