Activation of phosphoinositide catabolism and DNA synthesis in vascular smooth muscle cells by LDL and positively charged proteins: evidence that effects of LDL are not specifically dependent on the polycationic nature of apo B.
We have investigated whether the polycationic structure of apo B is an important determinant for the recognition of low density lipoprotein (LDL) by putative signalling-coupled/growth receptor(s). Using cultures of human vascular smooth muscle cells (VSMC), the effects of LDL on phosphoinositide (PI) catabolism and DNA synthesis have been compared with those of a variety of proteins which, like apo B, possess a strong positive charge. Using myo-[2-3H]-inositol-prelabelled VSMC, the polycationic proteins protamine and histones II-S, III-S, V-S and VII-S, but not low-molecular weight polyamines (putrescine and spermine), were found to stimulate PI catabolism in a dose- and time-dependent manner. In contrast to LDL which induced rapid, transient increases in inositol tris- and bis-phosphates and a delayed sustained increase in inositol monophosphate, the PI response of VSMC to polycationic proteins was characterized by a potent, sustained increase in inositol bisphosphate and the absence of an inositol trisphosphate transient. Heparin inhibited the PI catabolic response of VSMC to histones and protamine but was without effect on LDL-stimulated PI catabolism. Like LDL, polycationic proteins also stimulated DNA synthesis in VSMC (incorporation of [3H]-thymidine). The data indicate that signalling/growth effects of LDL and positively charged protein occur via distinct mechanisms and that the effects of LDL do not primarily depend upon the polycationic properties of apo B.
Resink
T
T
Department of Research, Basel University Hospital, Switzerland.
Tkachuk
V
V
Hahn
A
A
Bochkov
V
V
D001055:Apolipoproteins B / Q000737:chemistry / Q000494:pharmacology*; D001160:Arterioles; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006657:Histones / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009852:Omentum / Q000098:blood supply; D010716:Phosphatidylinositols / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D011479:Protamines / Q000494:pharmacology; D011700:Putrescine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors
D001055:Apolipoproteins B; D006657:Histones; D008074:Lipoproteins; D010716:Phosphatidylinositols; D011073:Polyamines; D011479:Protamines; D013096:Spermine; D004247:DNA; D011700:Putrescine