Increased Sensitivity of Histidinemic Mice to UVB Radiation Suggests a Crucial Role of Endogenous Urocanic Acid in Photoprotection

Urocanic acid (UCA) is produced by the enzyme histidase and accumulates in the stratum corneum of the epidermis. In this study, we investigated the photoprotective role of endogenous UCA in the murine skin using histidinemic mice, in which the gene encoding histidase is mutated. Histidase was detect...

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Bibliographic Details
Published in:Journal of investigative dermatology 2011-01, Vol.131 (1), p.188-194
Main Authors: Barresi, Caterina, Stremnitzer, Caroline, Mlitz, Veronika, Kezic, Sanja, Kammeyer, Arthur, Ghannadan, Minoo, Posa-Markaryan, Katja, Selden, Clare, Tschachler, Erwin, Eckhart, Leopold
Format: Article
Language:English
Subjects:
Amino Acid Metabolism, Inborn Errors - genetics
Amino Acid Metabolism, Inborn Errors - metabolism
Amino Acid Metabolism, Inborn Errors - pathology
Animals
Apoptosis - physiology
Apoptosis - radiation effects
Biological and medical sciences
Dermatology
DNA Damage - physiology
Epidermis - enzymology
Epidermis - pathology
Epidermis - radiation effects
Histidine Ammonia-Lyase - deficiency
Histidine Ammonia-Lyase - genetics
Histidine Ammonia-Lyase - metabolism
Intellectual Disability - genetics
Intellectual Disability - metabolism
Intellectual Disability - pathology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Phenotype
Pyrimidine Dimers - metabolism
Ultraviolet Rays - adverse effects
Urocanic Acid - metabolism
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Summary:Urocanic acid (UCA) is produced by the enzyme histidase and accumulates in the stratum corneum of the epidermis. In this study, we investigated the photoprotective role of endogenous UCA in the murine skin using histidinemic mice, in which the gene encoding histidase is mutated. Histidase was detected by immunohistochemistry in the stratum granulosum and stratum corneum of the normal murine skin but not in the histidinemic skin. The UCA content of the stratum corneum and the UVB absorption capacity of aqueous extracts from the stratum corneum were significantly reduced in histidinemic mice as compared with wild-type mice. When the shaved back skin of adult mice was irradiated with 250mJcm-2 UVB, histidinemic mice accumulated significantly more DNA damage in the form of cyclobutane pyrimidine dimers than did wild-type mice. Furthermore, UVB irradiation induced significantly higher levels of markers of apoptosis in the epidermis of histidinemic mice. Topical application of UCA reversed the UVB-photosensitive phenotype of histidinemic mice and increased UVB photoprotection of wild-type mice. Taken together, these results provide strong evidence for an important contribution of endogenous UCA to the protection of the epidermis against the damaging effects of UVB radiation.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2010.231