TY - JOUR
T1 - Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival
AU - Peus, Dominik
AU - Meves, Alexander
AU - Pott, Markus
AU - Beyerle, Astrid
AU - Pittelkow, Mark R.
N1 - Funding Information:
Dr. Peus was supported by the Deutsche Forschungsgemeinschaft (DFG) (PE 635/2-1) and by the Theodor-Nasemann Scholarship. Dr. Meves was supported by the German-American Fulbright Commission and the Studienstiftung des Deutschen Volkes. Additional support was provided by the Mayo Foundation. The excellent technical assistance provided by K. Squillace and M. Anderson is gratefully acknowledged.
PY - 2001/2/15
Y1 - 2001/2/15
N2 - 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.
AB - 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.
KW - Cell survival
KW - Free radicals
KW - Mitogen-activated protein kinase
KW - Reactive oxygen species
KW - Signaling
KW - Trolox
KW - Ultraviolet radiation
KW - Vitamin E
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U2 - 10.1016/S0891-5849(00)00488-3
DO - 10.1016/S0891-5849(00)00488-3
M3 - Article
C2 - 11182298
AN - SCOPUS:0035865773
SN - 0891-5849
VL - 30
SP - 425
EP - 432
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 4
ER -