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 Citations (Scopus)

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

Fingerprint

Vitamin E
Cell Survival
Chemical activation
Cells
Phosphotransferases
Keratinocytes
Epidermal Growth Factor Receptor
Antioxidants
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
Signal transduction
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Radiation Effects
Cell death
Ultraviolet radiation
Reactive Oxygen Species
Signal Transduction
Skin
Cell Death
Modulation

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

Cite this

Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival. / Peus, Dominik; Meves, Alexander; Pott, Markus; Beyerle, Astrid; Pittelkow, Mark R.

In: Free Radical Biology and Medicine, Vol. 30, No. 4, 15.02.2001, p. 425-432.

Research output: Contribution to journalArticle

Peus, Dominik ; Meves, Alexander ; Pott, Markus ; Beyerle, Astrid ; Pittelkow, Mark R. / Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival. In: Free Radical Biology and Medicine. 2001 ; Vol. 30, No. 4. pp. 425-432.
@article{8db01359996b4450935a756fef385dbc,
title = "Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival",
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.",
keywords = "Cell survival, Free radicals, Mitogen-activated protein kinase, Reactive oxygen species, Signaling, Trolox, Ultraviolet radiation, Vitamin E",
author = "Dominik Peus and Alexander Meves and Markus Pott and Astrid Beyerle and Pittelkow, {Mark R.}",
year = "2001",
month = "2",
day = "15",
doi = "10.1016/S0891-5849(00)00488-3",
language = "English (US)",
volume = "30",
pages = "425--432",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "4",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=0035865773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035865773&partnerID=8YFLogxK

U2 - 10.1016/S0891-5849(00)00488-3

DO - 10.1016/S0891-5849(00)00488-3

M3 - Article

C2 - 11182298

AN - SCOPUS:0035865773

VL - 30

SP - 425

EP - 432

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 4

ER -