VITAMIN-E - A SENSOR AND AN INFORMATION TRANSDUCER OF THE CELL OXIDATION-STATE

We studied the effects of RRR-alpha-tocopherol and RRR-beta-tocopherol in smooth muscle cells from rat (line A7r5) and human aortas. RRR-alp ha-Tocopherol, but not RRR-beta-tocopherol, inhibited smooth muscle ce ll proliferation in a dose-dependent manner at concentrations in the r ange from 10 to 50 mu mol/L. RRR-beta-Tocopherol added simultaneously with RRR-alpha-tocopherol prevented growth inhibition. The earliest ev ent brought about by RRR-alpha-tocopherol in the signal transduction c ascade controlling receptor-mediated cell growth was the activation of the transcription factor AP-1. RRR-beta-tocopherol alone was without effect but in combination with RRR-alpha-tocopherol prevented the AP-1 activating effect of the latter. Protein kinase C was inhibited by RR R-alpha-tocopherol and not by RRR-beta-tocopherol, which also in this case prevented the effect of RRR-alpha-tocopherol. Calyculin A, a prot ein phosphatase inhibitor, prevented the effect of RRR-alpha-tocophero l on protein kinase C. The data can be rationalized by a model in whic h a tocopherol-binding protein discriminates between RRR-alpha-tocophe rol and RRR-beta-tocopherol and initiates a cascade of events at the l evel of cell signal transduction that leads to the inhibition of cell proliferation.