Kinetics of 125I-PDGF binding and down-regulation of PDGF receptor in arterial smooth muscle cells derived from patients with moyamoya disease.
Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. We recently found that cultured smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease responded poorly to serum mitogens, especially to platelet-derived growth factor (PDGF). In the present study, we investigated further the binding and processing of 125I-PDGF, as well as down-regulation of the PDGF receptor in arterial SMC derived from patients with moyamoya disease. The specific binding sites of 125I-PDGF were reduced significantly at both 4 degrees C and 22 degrees C on SMC from moyamoya disease compared with those from control (4.78 vs. 11.92 x 10(4)/cell at 4 degrees C), though the apparent dissociation constant (Kd) were the same. Kinetics of 125I-PDGF binding at 37 degrees C in cells from moyamoya disease showed fewer binding sites (less than 1/3 of controls) and lower degradation per cell than in those from controls, though no difference was observed in either internalization or degradation of each receptor. When SMC were exposed to lower concentrations of nonlabeled PDGF at 37 degrees C, the percentage of remaining binding sites on cells from moyamoya disease was significantly less than that from controls. This excess down-regulation of PDGF receptor in SMC from moyamoya disease may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These results are closely correlated with the diminished proliferation responses to PDGF in SMC from moyamoya disease and provide evidence that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.
Aoyagi
M
M
Department of Cell Biology, Tokyo Metropolitan Institute of Gerontology, Japan.
Fukai
N
N
Matsushima
Y
Y
Yamamoto
M
M
Yamamoto
K
K
D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D006801:Humans; D007700:Kinetics; D009072:Moyamoya Disease / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor