Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival

Dominik Peus, Alexander Meves, Markus Pott, Astrid Beyerle, Mark R. Pittelkow

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

We have recently shown that exposure of human keratinocytes to physiologic doses of ultraviolet B (UVB) activates epidermal growth factor receptor (EGFR)/extracellular-regulated kinases 1 and 2 (ERK1/2) and p38 signaling pathways via reactive oxygen species, an effect that can be modulated by antioxidants. Trolox, a water-soluble vitamin E analog, is among the antioxidants that are currently being investigated for their preventive and protective potential against harmful effects of UV radiation to the skin. We found that Trolox inhibits both basal and UVB-induced intracellular H2O2 generation in primary keratinocytes in a concentration-dependent manner. Trolox did not significantly affect UVB-induced phosphorylation of EGFR. Stronger inhibition was observed for ERK1/2 activation at lower, and for p38 activation at higher, concentrations of Trolox added to cells before exposure to UVB. Similarly different effects were found with regard to length of pretreatment with Trolox before UVB exposure - increasing inhibition for ERK1/2 activation at shorter, and for p38 activation at longer, pretreatment intervals. UVB-induced c-jun-N-terminal kinase activation was potently suppressed by Trolox. Also, increasing the pretreatment time of Trolox decreased the rate of cell death following UVB. In conclusion, UVB-induced signaling pathway activation is differentially modulated by Trolox. Further investigation into the time-dependent biologic activation of Trolox and its metabolic products, and modulation of signal transduction with cell outcome should facilitate development of rational strategies for pharmacologic applications.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalFree Radical Biology and Medicine
Volume30
Issue number4
DOIs
StatePublished - Feb 15 2001

Keywords

  • Cell survival
  • Free radicals
  • Mitogen-activated protein kinase
  • Reactive oxygen species
  • Signaling
  • Trolox
  • Ultraviolet radiation
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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