Skip Navigation


Carcinogenesis Advance Access originally published online on November 4, 2007
Carcinogenesis 2008 29(1):219-225; doi:10.1093/carcin/bgm242
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
29/1/219    most recent
bgm242v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Black, A. T.
Right arrow Articles by Laskin, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Black, A. T.
Right arrow Articles by Laskin, J. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Distinct effects of ultraviolet B light on antioxidant expression in undifferentiated and differentiated mouse keratinocytes

Adrienne T. Black, Joshua P. Gray, Michael P. Shakarjian1, Debra L. Laskin, Diane E. Heck and Jeffrey D. Laskin2,*

Department of Pharmacology and Toxicology, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA
1 Department of Medicine
2 Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA

* To whom correspondence should be addressed. Tel: +732 445 0170; Fax: +732 445 0119; Email: jlaskin{at}eohsi.rutgers.edu

Ultraviolet (UV) B causes oxidative stress, which has been implicated in carcinogenesis. We determined if the sensitivity of keratinocytes to UVB-induced oxidative stress is dependent on their differentiation state. In primary cultures of undifferentiated and differentiated mouse keratinocytes, UVB (25 mJ/cm2) stimulated production of reactive oxygen intermediates. This was associated with increased messenger RNA (mRNA) expression of the antioxidant enzymes glutathione peroxidase, heme oxygenase-1 (HO-1) and the glutathione S-transferase (GST), GSTA1–2. The effects of UVB on GSTA1–2 were greater in undifferentiated when compared with differentiated cells. UVB also induced GSTM1, but only in undifferentiated cells. In contrast, UVB reduced expression of manganese superoxide dismutase, metallothionein-2, GSTA3 and microsomal glutathione S-transferase (mGST)3 in both cell types, whereas it had no major effects on catalase, copper–zinc superoxide dismutase, GSTP1, mGST1 or mGST2. Of note, levels of GSTA4 mRNA were 4- to 5-fold greater in differentiated relative to undifferentiated cells. Moreover, whereas GSTA4 was induced by UVB in undifferentiated cells, it was inhibited in differentiated cells. UVB activated p38 and c-jun N-terminal kinase mitogen-activated protein (MAP) kinases in both undifferentiated and differentiated keratinocytes. Whereas inhibition of these kinases blocked UVB-induced HO-1 in both cell types, GSTA1–2 and GST-4 were only suppressed in undifferentiated cells. In differentiated keratinocytes, p38 inhibition also suppressed GSTA1–2. In contrast, MAP kinase inhibition had no major effects on UVB-induced suppression of GSTA4 in differentiated cells. These data indicate that UVB-induced alterations in antioxidant expression are differentiation dependent. Moreover, MAP kinases are critical regulators of this response. Alterations in antioxidants are likely to be important mechanisms for protecting the skin from UVB-induced oxidative stress.

Abbreviations: COX-2, cyclooxygenase-2; Cu,Zn-SOD, copper–zinc superoxide dismutase; ERK, extracellular signal-regulated kinase; GPx, glutathione peroxidase; GST, glutathione S-transferase; HO-1, heme oxygenase-1; IL, interleukin; JNK, c-jun N-terminal kinase; MAP, mitogen-activated protein; mGST, microsomal glutathione S-transferase; mRNA, messenger RNA; Mn-SOD, manganese superoxide dismutase; MT-2, metallothionein-2; PCR, polymerase chain reaction; ROI, reactive oxygen intermediate; SOD, superoxide dismutase; TNF-{alpha}, tumor necrosis factor-{alpha}; UV, ultraviolet

Received May 9, 2007; revised October 23, 2007; accepted October 24, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.