Vitamin E: a sensor and an information transducer of the cell oxidation state

ABSTRACT We studied the effects of RRR-a-tocopherol and RRR-(3-tocopherol in smooth muscle cells from rat (line A7r5) and human aortas. RRR-a-Tocopherol, but not RRR-13-tocopherol, in-hibited smooth muscle cell proliferation in a dose-dependent man-ner at concentrations in the range from 10 to 50 .tmolIL. RRR-13-Tocopherol added simultaneously with RRR-a-tocopherol prevented growth inhibition. The earliest event brought about by RRR-a-tocopherol in the signal transduction cascade controlling receptor-mediated cell growth was the activation of the transcrip-tion factor AP- 1. RRR-/3-tocopherol alone was without effect but in combination with RRR-a-tocopherol prevented the AP-I acti-vating effect of the latter. Protein kinase C was inhibited by RRR-a-tocopherol and not by RRR-13-tocopherol, which also in this case prevented the effect of RRR-a-tocopherol. Calyculin A, a protein phosphatase inhibitor, prevented the effect of RRR-a-tocopherol on protein kinase C. The data can be rationalized by a model in which a tocopherol-binding protein discriminates be-tween RRR-a-tocopherol and RRR-f3-tocopherol and initiates a cascade of events at the level of cell signal transduction that leads to the inhibition of cell proliferation. Am J C/in Nuir 1995; 62(suppl): I 3375-465. KEY WORDS RRR-a-tocopherol, vitamin E, protein ki-nase C, vascular smooth muscle cells, AP- I transcription fac-tor, cell proliferation, oxidative stres