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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3420-3427.)
© 1997 American Heart Association, Inc.

Articles

Inhibition of Platelet-Derived Growth Factor BB–Induced Expression of Glyceraldehyde- 3-Phosphate Dehydrogenase by Sodium Butyrate in Rat Vascular Smooth Muscle Cells

Kasturi Ranganna; ; Frank M. Yatsu

From the Department of Neurology, University of Texas—Houston School of Medicine, Houston, Tex.

Correspondence to Kasturi Ranganna, Department of Neurology, University of Texas—Houston School of Medicine, 6431 Fannin, Suite 7.044, Houston TX 77030.

Abstract 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.

Key Words: glyceraldehyde-3-phosphate dehydrogenase • sodium butyrate • platelet-derived growth factor • smooth muscle cells • mRNA

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