UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes

Dominik Peus, Renius A. Vasa, Astrid Beyerle, Alexander Meves, Carsten Krautmacher, Mark R. Pittelkow

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

We have previously shown that hydrogen peroxide is an important mediator of ultraviolet B induced phosphorylation of the epidermal growth factor receptor in human keratinocytes. Here we demonstrate that physiologic doses of ultraviolet B and hydrogen peroxide stimulate activation of two related but distinct mitogen-activated protein kinase pathways: extracellular regulated kinase 1 and 2 (ERK1/2), as well as p38, the mammalian homolog of HOG1 in yeast which is a major kinase for a recently identified stress- induced signaling pathway. The time-dependent activation of ERK1/2 and p38 are distinct, and ultraviolet B-induced ERK1/2 activation is downregulated more rapidly than p38. Using dihydrorhodamine or Amplex as specific fluorescent dye probes, we show that ultraviolet B-induced peroxides can be inhibited by ascorbic acid. Ascorbic acid strongly blocks ERK1/2 and p38 activation by ultraviolet B and hydrogen peroxide whereas pyrrolidine dithiocarbamate and butyl hydroxyanisole are less effective. Pyrrolidine dithiocarbamate was unable to inhibit ultraviolet B-induced p38 activation. Cell death was increased after ultraviolet B when ERK1/2 activation was attenuated by the specific inhibitor PD098059. The distinct time courses and extents of activation and inhibition of ERK1/2 and p38 indicate that these pathways are separate and regulated independently in keratinocytes. Specific types of reactive oxygen species induced by ultraviolet B as well as selective activation or inhibition of specific phosphatases may mediate these responses in keratinocytes. These findings demonstrate that reactive oxygen species are important multifunctional mediators of ultraviolet B-induced ERK1/2 and p38 signaling transduction pathways and suggest that ERK1/2 may play an important part in protecting keratinocytes from cell death following oxidative stress.

Original languageEnglish (US)
Pages (from-to)751-756
Number of pages6
JournalJournal of Investigative Dermatology
Volume112
Issue number5
DOIs
StatePublished - Jan 1 1999

Fingerprint

Keratinocytes
Reactive Oxygen Species
Phosphotransferases
Chemical activation
Hydrogen Peroxide
Cell death
Fluorescent Dyes
Ascorbic Acid
Cell Death
Phosphorylation
Oxidative stress
Peroxides
Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Epidermal Growth Factor Receptor
Yeast
Oxidative Stress
Down-Regulation
Yeasts

Keywords

  • Extracellular regulated kinase
  • Hydrogen peroxide
  • Keratinocytes
  • Mitogen- activated protein kinase
  • P38
  • Reactive oxygen species
  • Ultraviolet B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. / Peus, Dominik; Vasa, Renius A.; Beyerle, Astrid; Meves, Alexander; Krautmacher, Carsten; Pittelkow, Mark R.

In: Journal of Investigative Dermatology, Vol. 112, No. 5, 01.01.1999, p. 751-756.

Research output: Contribution to journalArticle

Peus, Dominik ; Vasa, Renius A. ; Beyerle, Astrid ; Meves, Alexander ; Krautmacher, Carsten ; Pittelkow, Mark R. / UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. In: Journal of Investigative Dermatology. 1999 ; Vol. 112, No. 5. pp. 751-756.
@article{75412aa1ba09423fb7c216d3360a8e03,
title = "UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes",
abstract = "We have previously shown that hydrogen peroxide is an important mediator of ultraviolet B induced phosphorylation of the epidermal growth factor receptor in human keratinocytes. Here we demonstrate that physiologic doses of ultraviolet B and hydrogen peroxide stimulate activation of two related but distinct mitogen-activated protein kinase pathways: extracellular regulated kinase 1 and 2 (ERK1/2), as well as p38, the mammalian homolog of HOG1 in yeast which is a major kinase for a recently identified stress- induced signaling pathway. The time-dependent activation of ERK1/2 and p38 are distinct, and ultraviolet B-induced ERK1/2 activation is downregulated more rapidly than p38. Using dihydrorhodamine or Amplex as specific fluorescent dye probes, we show that ultraviolet B-induced peroxides can be inhibited by ascorbic acid. Ascorbic acid strongly blocks ERK1/2 and p38 activation by ultraviolet B and hydrogen peroxide whereas pyrrolidine dithiocarbamate and butyl hydroxyanisole are less effective. Pyrrolidine dithiocarbamate was unable to inhibit ultraviolet B-induced p38 activation. Cell death was increased after ultraviolet B when ERK1/2 activation was attenuated by the specific inhibitor PD098059. The distinct time courses and extents of activation and inhibition of ERK1/2 and p38 indicate that these pathways are separate and regulated independently in keratinocytes. Specific types of reactive oxygen species induced by ultraviolet B as well as selective activation or inhibition of specific phosphatases may mediate these responses in keratinocytes. These findings demonstrate that reactive oxygen species are important multifunctional mediators of ultraviolet B-induced ERK1/2 and p38 signaling transduction pathways and suggest that ERK1/2 may play an important part in protecting keratinocytes from cell death following oxidative stress.",
keywords = "Extracellular regulated kinase, Hydrogen peroxide, Keratinocytes, Mitogen- activated protein kinase, P38, Reactive oxygen species, Ultraviolet B",
author = "Dominik Peus and Vasa, {Renius A.} and Astrid Beyerle and Alexander Meves and Carsten Krautmacher and Pittelkow, {Mark R.}",
year = "1999",
month = "1",
day = "1",
doi = "10.1046/j.1523-1747.1999.00584.x",
language = "English (US)",
volume = "112",
pages = "751--756",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes

AU - Peus, Dominik

AU - Vasa, Renius A.

AU - Beyerle, Astrid

AU - Meves, Alexander

AU - Krautmacher, Carsten

AU - Pittelkow, Mark R.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - We have previously shown that hydrogen peroxide is an important mediator of ultraviolet B induced phosphorylation of the epidermal growth factor receptor in human keratinocytes. Here we demonstrate that physiologic doses of ultraviolet B and hydrogen peroxide stimulate activation of two related but distinct mitogen-activated protein kinase pathways: extracellular regulated kinase 1 and 2 (ERK1/2), as well as p38, the mammalian homolog of HOG1 in yeast which is a major kinase for a recently identified stress- induced signaling pathway. The time-dependent activation of ERK1/2 and p38 are distinct, and ultraviolet B-induced ERK1/2 activation is downregulated more rapidly than p38. Using dihydrorhodamine or Amplex as specific fluorescent dye probes, we show that ultraviolet B-induced peroxides can be inhibited by ascorbic acid. Ascorbic acid strongly blocks ERK1/2 and p38 activation by ultraviolet B and hydrogen peroxide whereas pyrrolidine dithiocarbamate and butyl hydroxyanisole are less effective. Pyrrolidine dithiocarbamate was unable to inhibit ultraviolet B-induced p38 activation. Cell death was increased after ultraviolet B when ERK1/2 activation was attenuated by the specific inhibitor PD098059. The distinct time courses and extents of activation and inhibition of ERK1/2 and p38 indicate that these pathways are separate and regulated independently in keratinocytes. Specific types of reactive oxygen species induced by ultraviolet B as well as selective activation or inhibition of specific phosphatases may mediate these responses in keratinocytes. These findings demonstrate that reactive oxygen species are important multifunctional mediators of ultraviolet B-induced ERK1/2 and p38 signaling transduction pathways and suggest that ERK1/2 may play an important part in protecting keratinocytes from cell death following oxidative stress.

AB - We have previously shown that hydrogen peroxide is an important mediator of ultraviolet B induced phosphorylation of the epidermal growth factor receptor in human keratinocytes. Here we demonstrate that physiologic doses of ultraviolet B and hydrogen peroxide stimulate activation of two related but distinct mitogen-activated protein kinase pathways: extracellular regulated kinase 1 and 2 (ERK1/2), as well as p38, the mammalian homolog of HOG1 in yeast which is a major kinase for a recently identified stress- induced signaling pathway. The time-dependent activation of ERK1/2 and p38 are distinct, and ultraviolet B-induced ERK1/2 activation is downregulated more rapidly than p38. Using dihydrorhodamine or Amplex as specific fluorescent dye probes, we show that ultraviolet B-induced peroxides can be inhibited by ascorbic acid. Ascorbic acid strongly blocks ERK1/2 and p38 activation by ultraviolet B and hydrogen peroxide whereas pyrrolidine dithiocarbamate and butyl hydroxyanisole are less effective. Pyrrolidine dithiocarbamate was unable to inhibit ultraviolet B-induced p38 activation. Cell death was increased after ultraviolet B when ERK1/2 activation was attenuated by the specific inhibitor PD098059. The distinct time courses and extents of activation and inhibition of ERK1/2 and p38 indicate that these pathways are separate and regulated independently in keratinocytes. Specific types of reactive oxygen species induced by ultraviolet B as well as selective activation or inhibition of specific phosphatases may mediate these responses in keratinocytes. These findings demonstrate that reactive oxygen species are important multifunctional mediators of ultraviolet B-induced ERK1/2 and p38 signaling transduction pathways and suggest that ERK1/2 may play an important part in protecting keratinocytes from cell death following oxidative stress.

KW - Extracellular regulated kinase

KW - Hydrogen peroxide

KW - Keratinocytes

KW - Mitogen- activated protein kinase

KW - P38

KW - Reactive oxygen species

KW - Ultraviolet B

UR - http://www.scopus.com/inward/record.url?scp=0032896873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032896873&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1747.1999.00584.x

DO - 10.1046/j.1523-1747.1999.00584.x

M3 - Article

VL - 112

SP - 751

EP - 756

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 5

ER -