Mitogenesis by serum and PDGF is independent of PI degradation and PKC in VSMC.
Capacities of serum, platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) on phosphatidylinositol (PI) degradation and cell growth were compared in cultured vascular smooth muscle cells (VSMC) from rat aorta. The role of protein kinase C (PKC) in growth control was also evaluated using polymixin B, a selective inhibitor of PKC. Both dialyzed and nondialyzed fetal bovine serum (FBS) in concentrations from 2 to 20% stimulated [3H]thymidine incorporation into DNA and cell growth without producing corresponding increases in PI turnover. Moreover, both PDGF (40-160 ng/ml) and FGF (6.25-150 ng/ml) also stimulated mitogenesis, but PDGF was more effective although less potent. Mitogenic amounts of PDGF did not stimulate PI turnover, whereas a maximally mitogenic amount of FGF (50 ng/ml) did produce a slight increase. Polymixin B inhibited PKC activity (IC50, 32 microM) from these cells but failed to suppress DNA synthesis produced by 10% FBS or PDGF (50 ng/ml). However, it did suppress that by FGF (50 ng/ml). Angiotensin II (10(-11)-10(-7) M) and phorbol 12,13-dibutyrate (PDB, 1-20 nM) were not mitogenic in the presence or absence of insulin (10 micrograms/ml) or the calcium ionophore A23187 (0.25-4 microM), under serum-free conditions. Instead, PDB inhibited mitogenesis of cells maintained under 0.2% FBS or stimulated with insulin (10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Kihara
M
M
Merrell Dow Research Institute, Cincinnati 45215.
Robinson
P J
PJ
Buck
S H
SH
Dage
R C
RC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001769:Blood; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003956:Dialysis; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D005346:Fibroblast Growth Factors; D004247:DNA; D011493:Protein Kinase C; D011112:Polymyxin B