Acute Hyperglycemia Regulates Transcription and Posttranscriptional Stability of PKCβII MRNA in Vascular Smooth Muscle Cells
A10 cells, human AoSMC, acute hyperglycemia, posttranscriptional regulation, glucose
Digital Object Identifier (DOI)
Acute hyperglycemia may contribute to the progression of atherosclerosis by regulating protein kinase C (PKC) isozymes and by accelerating vascular smooth muscle cell (VSMC) proliferation. We investigated acute glucose regulation of PKCβ gene expression in A10 cells, a rat aortic smooth muscle cell line. Western blot analysis showed that PKCβII protein levels decreased with high glucose (25 mM) compared to normal glucose (5.5 mM), whereas PKCβI levels were unaltered. PKCβ mRNA levels were depleted by 60–75% in hyperglycemic conditions. To elucidate whether high glucose regulated PKCβ expression via the common promoter for PKCβI and PKCβII, deletion constructs of the PKCβ promoter ligated to CAT as reporter gene were transfected into A10 cells. Construct D (−411 to + 179CAT) showed quenching in high glucose (25 mM) and suggested the involvement of a carbohydrate response element in the 5′ promoter region of the PKCβ gene. In actinomycin D-treated A10 cells, a 60% decrease in PKCβ mRNA with high glucose treatment indicated that posttranscriptional destabilization by glucose was also occurring. We have demonstrated that glucose-induced posttranscriptional destabilization of PKCβII message is mediated via a nuclease activity present in the cytosol. The specificity of glucose to post-transcriptionally destabilize PKCβII mRNA, but not the PKCβI mRNA, was confirmed in both A10 cells and primary cultures from human aorta.—Patel, N. A., Chalfant, C. E., Yamamoto, M., Watson, J. E., Eichler, D. C., Cooper, D. R. Acute hyperglycemia regulates transcription and posttranscriptional stability of PKCβII mRNA in vascular smooth muscle cells. FASEB J. 13, 103–113 (1999)
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Citation / Publisher Attribution
The FASEB Journal, v. 13, issue 1, p. 103-113
Scholar Commons Citation
Patel, Niketa A.; Chalfant, Charles E.; Yamamoto, Mayumi; Watson, James E.; Eichler, Duane C.; and Cooper, Denise R., "Acute Hyperglycemia Regulates Transcription and Posttranscriptional Stability of PKCβII MRNA in Vascular Smooth Muscle Cells" (1999). Molecular Medicine Faculty Publications. 77.