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Carcinogenesis Advance Access published online on November 4, 2007
Carcinogenesis, doi:10.1093/carcin/bgm242
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© 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. Black1, Joshua P. Gray1, Michael P. Shakarjian2, Debra L. Laskin1, Diane E. Heck1 and Jeffrey D. Laskin2,*

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

* To whom correspondence should be addressed Jeffrey D. Laskin, Ph.D., Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08854, Email: jlaskin{at}eohsi.rutgers.edu

UVB 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 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 to differentiated cells. UVB also induced GSTM1, but only in undifferentiated cells. In contrast, UVB reduced expression of Mn-superoxide dismutase (SOD), metallothionein-2, GSTA3 and microsomal GST3 in both cell types, whereas it had no major effects on catalase, Cu,Zn-SOD, GSTP1, microsomal GST1 or microsomal GST2. Of note, levels of GSTA4 mRNA were 4-5-fold greater in differentiated relative to undifferentiated cells. Moreover, while GSTA4 was induced by UVB in undifferentiated cells, it was inhibited in differentiated cells. UVB activated p38 and JNK 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.

Key Words: UVB • glutathione-S-transferase • MAPEG • hydrogen peroxide • skin • oxidative stress

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


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