Ultraviolet A induced modulation of gap junctional intercellular communication by P38 MAPK activation in human keratinocytes

Barbara Bellei, Arianna Mastrofrancesco, Stefania Briganti, Nicaela Aspite, Niloofar Ale-agha, Helmut Sies, Mauro Picardo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK). In this study, UVA irradiation (10 J/cm2) compromised GJIC integrity in absence of cytotoxic effects as demonstrated by the absence of cell death and by the reversibility of GJIC down-regulation. Inhibition of communication by UVA was associated with hyperphosphorylation and decreased expression of connexin43 (Cx43), the most abundant gap junction protein expressed by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part, mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and Ser282 sites, two downstream direct targets of p38 MAPK were found to be phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did not significantly protect from cell-cell communication inhibition because of a strong cellular cytotoxicity observed with SB202190 and SB203580, two selective inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity reduced both phosphorylation and degradation of Cx43, demonstrating that these events are correlated.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalExperimental Dermatology
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

p38 Mitogen-Activated Protein Kinases
Keratinocytes
Connexin 43
Chemical activation
Modulation
Communication
Connexins
Mitogen-Activated Protein Kinases
Cell Communication
Carcinogenesis
Phosphorylation
Oxidative Stress
Cell Death
Oxidative stress
Coloring Agents
Down-Regulation
Cell death
Cytotoxicity
Cell Line
Skin

Keywords

  • Connexin43
  • GJIC
  • Keratinocytes
  • MAPK
  • Mitogen-activated protein kinase
  • UVA

ASJC Scopus subject areas

  • Dermatology

Cite this

@article{f0da025647004b13bd611c59220e2dd3,
title = "Ultraviolet A induced modulation of gap junctional intercellular communication by P38 MAPK activation in human keratinocytes",
abstract = "Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK). In this study, UVA irradiation (10 J/cm2) compromised GJIC integrity in absence of cytotoxic effects as demonstrated by the absence of cell death and by the reversibility of GJIC down-regulation. Inhibition of communication by UVA was associated with hyperphosphorylation and decreased expression of connexin43 (Cx43), the most abundant gap junction protein expressed by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part, mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and Ser282 sites, two downstream direct targets of p38 MAPK were found to be phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did not significantly protect from cell-cell communication inhibition because of a strong cellular cytotoxicity observed with SB202190 and SB203580, two selective inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity reduced both phosphorylation and degradation of Cx43, demonstrating that these events are correlated.",
keywords = "Connexin43, GJIC, Keratinocytes, MAPK, Mitogen-activated protein kinase, UVA",
author = "Barbara Bellei and Arianna Mastrofrancesco and Stefania Briganti and Nicaela Aspite and Niloofar Ale-agha and Helmut Sies and Mauro Picardo",
year = "2008",
month = "2",
doi = "10.1111/j.1600-0625.2007.00662.x",
language = "English",
volume = "17",
pages = "115--124",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Ultraviolet A induced modulation of gap junctional intercellular communication by P38 MAPK activation in human keratinocytes

AU - Bellei, Barbara

AU - Mastrofrancesco, Arianna

AU - Briganti, Stefania

AU - Aspite, Nicaela

AU - Ale-agha, Niloofar

AU - Sies, Helmut

AU - Picardo, Mauro

PY - 2008/2

Y1 - 2008/2

N2 - Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK). In this study, UVA irradiation (10 J/cm2) compromised GJIC integrity in absence of cytotoxic effects as demonstrated by the absence of cell death and by the reversibility of GJIC down-regulation. Inhibition of communication by UVA was associated with hyperphosphorylation and decreased expression of connexin43 (Cx43), the most abundant gap junction protein expressed by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part, mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and Ser282 sites, two downstream direct targets of p38 MAPK were found to be phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did not significantly protect from cell-cell communication inhibition because of a strong cellular cytotoxicity observed with SB202190 and SB203580, two selective inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity reduced both phosphorylation and degradation of Cx43, demonstrating that these events are correlated.

AB - Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK). In this study, UVA irradiation (10 J/cm2) compromised GJIC integrity in absence of cytotoxic effects as demonstrated by the absence of cell death and by the reversibility of GJIC down-regulation. Inhibition of communication by UVA was associated with hyperphosphorylation and decreased expression of connexin43 (Cx43), the most abundant gap junction protein expressed by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part, mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and Ser282 sites, two downstream direct targets of p38 MAPK were found to be phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did not significantly protect from cell-cell communication inhibition because of a strong cellular cytotoxicity observed with SB202190 and SB203580, two selective inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity reduced both phosphorylation and degradation of Cx43, demonstrating that these events are correlated.

KW - Connexin43

KW - GJIC

KW - Keratinocytes

KW - MAPK

KW - Mitogen-activated protein kinase

KW - UVA

UR - http://www.scopus.com/inward/record.url?scp=38349056844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349056844&partnerID=8YFLogxK

U2 - 10.1111/j.1600-0625.2007.00662.x

DO - 10.1111/j.1600-0625.2007.00662.x

M3 - Article

VL - 17

SP - 115

EP - 124

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 2

ER -