Atypical low density lipoprotein binding site that may mediate lipoprotein-induced signal transduction.
The characteristics of low density lipoprotein (LDL) binding in quiescent cultures of human vascular smooth muscle cells (VSMC) have been further investigated and compared with the characteristics of high affinity LDL binding in human fibroblasts [via the apolipoprotein (apo) B/E receptor] and with the properties of LDL-induced phosphoinositide catabolism in VSMC. In VSMC the bulk of specific 125I-LDL binding occurs at a low affinity site, several characteristics of which are distinct from those of 125I-LDL binding to the apo B/E receptor in fibroblasts. (a) The affinity of LDL binding in VSMC is 25-50 times lower than that in fibroblasts (Kd approximately 50 micrograms/ml versus Kd approximately 2 micrograms/ml). (b) The kinetics of LDL association and dissociation in VSMC are more rapid than those in fibroblasts. (c) In contrast to apo B/E receptor-mediated binding of LDL in fibroblasts, binding of LDL to VSMC is insensitive to heparin, chemical modification of lysine residues, and chelation (with EDTA) of divalent cations. (d) Apo E-free high density lipoprotein 3 displaces labeled LDL more effectively in VSMC than in fibroblasts. (e) The ratio of bound/internalized LDL to degraded LDL differs markedly between fibroblasts and VSMC. LDL-stimulated phosphoinositide catabolism in VSMC, which occurs with an activation constant similar to the Kd for low affinity LDL binding, is insensitive to heparin, modification of lysine and arginine residues in LDL, and chelation of divalent cations. Thus, the atypical low affinity receptor in these cells may mediate the effects of LDL on signal transduction.
Tkachuk
V A
VA
Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Moscow, Russia.
Kuzmenko
Y S
YS
Resink
T J
TJ
Stambolsky
D V
DV
Bochkov
V N
VN
D001665:Binding Sites; D002478:Cells, Cultured; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D015398:Signal Transduction
D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D004492:Edetic Acid; D008239:Lysine