PHOSPHATIDYLINOSITOL 3-KINASE IS INVOLVED IN THE INDUCTION OF MACROPHAGE GROWTH BY OXIDIZED LOW-DENSITY-LIPOPROTEIN

Citation
Js. Martens et al., PHOSPHATIDYLINOSITOL 3-KINASE IS INVOLVED IN THE INDUCTION OF MACROPHAGE GROWTH BY OXIDIZED LOW-DENSITY-LIPOPROTEIN, The Journal of biological chemistry, 273(9), 1998, pp. 4915-4920
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4915 - 4920
Database
ISI
SICI code
0021-9258(1998)273:9<4915:P3IIIT>2.0.ZU;2-O
Abstract
Early atherosclerotic lesions are characterized by the presence of cho lesterol-rich, macrophage-derived foam cells. It has recently been sho wn that macrophage proliferation occurs during the development of earl y lesions and that oxidized low density lipoprotein (LDL) stimulates m acrophage growth, Possible mechanisms for this induction of macrophage growth include potentiation of mitogenic signal transduction by a com ponent of oxidized LDL following internalization and degradation, inte raction with integral plasma membrane proteins coupled to signaling pa thways, or direct or indirect activation of growth factor receptors on the cell surface (e.g. GM-CSF receptor) through an autocrine/paracrin e mechanism, The present study was undertaken to characterize some of the early intracellular signaling events by which oxidized LDL mediate s macrophage cell growth. Extensively oxidized LDL increased protein-t yrosine phosphorylation and caused a 2-fold increase in phosphatidylin ositol (PI) 3-kinase activity in phorbol ester-pretreated THP-1 cells (a human monocyte-like cell line). Similar concentrations of native LD L had no effect. Oxidized LDL also stimulated growth of resident mouse peritoneal macrophages, and this effect was reduced by 40-50% in cell s treated with PI 3-kinase inhibitors (100 nM wortmannin or 20 mu M LY 294002), These results suggest that PI 3-kinase mediates part of the m itogenic effect of oxidized LDL, but parallel pathways involving other receptors and signal transduction pathways are likely also involved.