The effect of alpha-tocopherol on the synthesis, phosphorylation and activity of protein kinase C in smooth muscle cells after phorbol 12-myristate 13-acetate down-regulation.
Previous work had established that, in smooth muscle cells, alpha-tocopherol negatively regulates protein kinase C by preventing its activation [Tasinato, A., Boscoboinik, D., Bartoli, G. M., Maroni, P. & Azzi, A. (1995) Proc. Natl Acad. Sci. USA 92, 12190-12194]. In this study, the mechanism by which this event takes place has been analyzed. The regulation by alpha-tocopherol of protein kinase C expression, activity and phosphorylation has been followed during the synthesis of protein kinase C after its down-regulation by phorbol 12-myristate 13-acetate. The data show that protein kinase C isoenzyme alpha is synthesised significantly more (30% 72 h after down-regulation) in the presence of alpha-tocopherol. However, its activity is significantly less (45% diminution) and its phosphorylation state is also decreased (60% diminution). The effect of alpha-tocopherol appears not to be shared by the analogue beta-tocopherol, provided with similar radical-scavenging properties. The data are interpreted in terms of a diminution of protein kinase C phosphorylation, specifically caused by alpha-tocopherol, resulting in a decreased enzyme specific activity.
Clément
S
S
Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.
Tasinato
A
A
Boscoboinik
D
D
Azzi
A
A
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism; D009130:Muscle, Smooth / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000378:metabolism; D051571:Protein Kinase C-alpha; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D007527:Isoenzymes; D014810:Vitamin E; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate