Vitamin E Inhibits the Activation of Protein Kinase C Involved in Monocyte Activation and Cell Proliferation
Catherine Pasquier, Jamel El Benna.
INSERM U479, CHU X. Bichat, Paris, France
Vitamin E, (vit E) is an antioxidant able to prevent the propagation of free radical damage of biological membranes, by its peroxyl radical scavenger property. Its effects is mainly due to its chain-breaking capacity. It is able to stop the peroxidation of LDL where vitamin E has an important antioxidant effect. Vitamin E is the collective name for eight naturally occuring molecules, four tocopherols and four tocotrienols. Tocotrienols differ from tocopherols in that they have an unsaturated phytyl side chain; the four forms of tocopherols and tocotrienols differ in the number of methyl groups on the chromanol nucleus (a- has 3, b- and g- have 2, whereas d- has 1). The biological activity of the various vitamine E forms roughly correlate with their antioxidant activities; the  order of relative peroxyl  radical reactivities of a-, b-, g-, and d-tocopherols is the same as the relative order of their biological activities. However, this correlation is not really conserved for all of these molecules, as for example a-tocotrienol, has only one third the scavenging biological activity of a-tocopherol but has higher or equivalent antioxidant activity. Indeed, it has been shown in various cellular types that a-tocopherol was not only an antioxidant but was also able to inhibit Protein Kinase C (PKC), a kinase involved in a lot of cellular functions such as cell proliferation and migration. We show here that a-tocopherol is able to inhibit the production of superoxide anion by adherent monocytes, stimulated by a phorbol ester compound (PMA). This inhibition is correlated with a decrease in phosphorylation of p47phox, a component of the enzyme NADPH oxidase. These results suggest an inhibition of PKC by vit E. Its mechanism of action could be due to an interaction of a-tocopherol with PKC in the membrane. However, in smooth muscle cells it has been shown that the inhibitory effect of vit E on PKC activity was due to the activation of a phosphatase.