Inhibition of platelet-derived growth factor BB-induced expression of glyceraldehyde-3-phosphate dehydrogenase by sodium butyrate in rat vascular smooth muscle cells.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key regulatory enzyme of glycolysis, which exists in nuclei and functions as a DNA-binding protein as well as a nuclear protein, appears to be modulated by cellular activities. Exposure of quiescent rat smooth muscle cells (SMCs) to platelet-derived growth factor BB (PDGF-BB), which stimulates SMCs proliferation, caused a time-dependent increase in mRNA for GAPDH and its catalytic activity. Treatment of quiescent SMCs with sodium butyrate (SB), which is shown to inhibit PDGF-BB-induced SMC proliferation, caused a time- and concentration-dependent decrease in PDGF-BB-induced GAPDH mRNA expression and its catalytic activity. Nuclear run-on studies revealed that the PDGF-BB-induced rate of GAPDH gene transcription was reduced by about 50% in the presence of 5 mmol/L SB. The protein synthesis inhibitor, cycloheximide, failed to abolish the SB-inhibited PDGF-BB-induced rate of transcription of GAPDH, suggesting that SB is not dependent on ongoing protein synthesis to exert its effects on PDGF-BB-induced GAPDH transcription. Furthermore, measurement of GAPDH mRNA stability at various times after the inhibition of transcription with actinomycin D indicated that 5 mmol/L SB has no significant effect on the half-life of PDGF-BB-induced mRNA. The reduction in PDGF-BB-induced GAPDH expression by SB is probably caused by a cycloheximide-insensitive transcriptional mechanism. Thus, the inhibition of PDGF-BB-induced expression of GAPDH by SB suggests a link between SMC proliferation, energy consumption, and GAPDH gene upregulation.
Ranganna
K
K
Department of Neurology, University of Texas-Houston School of Medicine, Houston 77030, USA.
Yatsu
F M
FM
D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D002087:Butyrates; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D003609:Dactinomycin; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases