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
AU - Berliner, Judith A.
AU - Subbanagounder, Ganesamoorthy G.
AU - Bhunia, Anil K.
AU - Koh, Steve
N1 - Funding Information:
This work was supported by a NIH Grant R01 DK-31722 1 P50 HL47212 (SC) and HL-30568(JB). We would like to the skillful assistance of Mrs. Pauline Gugliotta and Nancy Wong in the preparation of this manuscript.
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
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U2 - 10.1023/B:GLYC.0000033629.54962.68
DO - 10.1023/B:GLYC.0000033629.54962.68
M3 - Article
C2 - 15229397
AN - SCOPUS:3543099692
SN - 0282-0080
VL - 20
SP - 331
EP - 338
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 5
ER -