Signalling functions of alpha-tocopherol in smooth muscle cells.
alpha-Tocopherol but not beta-tocopherol, activates protein phosphatase 2A, decreases protein kinase C activity and attenuates smooth muscle cell proliferation at physiological concentrations. beta-Tocopherol prevents the effects of alpha-tocopherol. Inhibition of protein kinase C alpha, but not of the other isoforms, by the inhibitor Gö6976 prevents the effect of alpha-tocopherol. Protein kinase C alpha, immunoprecipitated from alpha-tocopherol treated cells, is less phosphorylated and inactive. It is proposed that the specific activation of protein phosphatase 2A by alpha-tocopherol results in dephosphorylation and inactivation of protein kinase C alpha. Finally, this cascade of events leads to smooth muscle cell proliferation inhibition.
Azzi
A
A
Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.
Boscoboinik
D
D
Clément
S
S
Ozer
N K
NK
Ricciarelli
R
R
Stocker
A
A
Tasinato
A
A
Sirikçi
O
O
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009994:Osmolar Concentration; D010749:Phosphoprotein Phosphatases / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D054648:Protein Phosphatase 2; D011817:Rabbits; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D007527:Isoenzymes; D014810:Vitamin E; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D013755:Tetradecanoylphorbol Acetate