Acute hyperglycemia regulates transcription and posttranscriptional stability of PKC beta II mRNA in vascular smooth muscle cells

Citation
Na. Patel et al., Acute hyperglycemia regulates transcription and posttranscriptional stability of PKC beta II mRNA in vascular smooth muscle cells, FASEB J, 13(1), 1999, pp. 103-113
Citations number
44
Categorie Soggetti
Experimental Biology
Journal title
FASEB JOURNAL
ISSN journal
08926638 → ACNP
Volume
13
Issue
1
Year of publication
1999
Pages
103 - 113
Database
ISI
SICI code
0892-6638(199901)13:1<103:AHRTAP>2.0.ZU;2-H
Abstract
Acute hyperglycemia may contribute to the progression of atherosclerosis by regulating protein kinase C (PKC) isozymes and by accelerating vascular sm ooth muscle cell (VSMC) proliferation. We investigated acute glucose regula tion of PKC beta gene expression in A10 cells, a rat aortic smooth muscle c ell line. Western blot analysis showed that PKC beta II protein levels decr eased with high glucose (25 mM) compared to normal glucose (5.5 mM), wherea s PKC beta I levels were unaltered. PKC beta mRNA levels were depleted by 6 0-75% in hyperglycemic conditions. To elucidate whether high glucose regula ted PKC beta expression via the common promoter for PKCPI and PKC beta II, deletion constructs of the PKC beta promoter ligated to CAT as reporter gen e were transfected into A10 cells, Construct D (-411 to +179CAT) showed que nching in high glucose (25 mM) and suggested the involvement of a carbohydr ate response element in the 5' promoter region of the PKC beta gene. In act inomycin D-treated A10 cells, a 60% decrease in PKC beta mRNA with high glu cose treatment indicated that posttranscriptional destabilization by glucos e was also occurring, We have demonstrated that glucose-induced posttranscr iptional destabilization of PKC beta II message is mediated via a nuclease activity present in the cytosol, The specificity of glucose to posttranscri ptionally destabilize PKC beta II mRNA, but not the PKC beta I mRNA, was co nfirmed in both A10 cells and primary cultures from human aorta.