Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1alpha.
10.4196/kjpp.2010.14.2.91
- Author:
Young Suk CHO
1
;
Kyung Hoon LEE
;
Jong Wan PARK
Author Information
1. Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea.
- Publication Type:Original Article
- Keywords:
Ultraviolet;
Skin;
Hyperplasia;
Hypoxia-inducible factor-1alpha;
Pyrithione-zinc
- MeSH:
Animals;
Cell Cycle;
Epidermis;
Homeostasis;
Hyperplasia;
Keratinocytes;
Mice;
Skin;
Skin Diseases;
Skin Neoplasms
- From:The Korean Journal of Physiology and Pharmacology
2010;14(2):91-97
- CountryRepublic of Korea
- Language:English
-
Abstract:
Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-1alpha controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1alpha is down-regulated by UVB and that this process is involved in UVB-induced skin hyperplasia. Therefore, we hypothesized that the forced expression of HIF-1alpha in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1alpha, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1alpha in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1alpha protein in keratinocytes, while it did not affect the synthesis of HIF-1alpha. Moreover, the p21 cell cycle inhibitor was down-regulated after UVB exposure, but was robustly induced by Py-Zn. In mice repeatedly irradiated with UVB, the epidermis became hyperplastic and HIF-1alpha disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1alpha to the normal level. These results suggest that Py-Zn is a potential agent to prevent UVB-induced photoaging and skin cancer development. This work also provides insight into a molecular target for treatment of UVB-induced skin diseases.
