Increased expression of transglutaminase-1 and PPARγ after vitamin E treatment in human keratinocytes

In skin, vitamin E acts as the predominant lipophilic antioxidant with a protective function against irradiation and oxidative stress. In addition to that, vitamin E can also modulate signal transduction and gene expression. To study whether the four natural tocopherol analogues (-, -, -, -tocopherol) can inXuence transcriptional activity by modulating the activity of nuclear receptors, a human keratinocytes cell line (NCTC 2544) was transfected with plasmids containing the luciferase reporter gene under control by direct repeat elements (DR1–DR4), representing binding sites for four diVerent classes of nuclear receptors. In this model, the tocopherols positively modulated only the reporter construct containing a consensus element for peroxisome proliferator-activated receptors (PPARs). The induction was strongest with -tocopherol and was most likely the direct consequence of stimulation of PPAR protein expression in keratinocytes. Vitamin E treatment also led to increased expression of a known PPAR target gene involved in terminal keratinocytes differentiation, the transglutaminase-1.