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 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 250 mJ cm(-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.
Barresi
Caterina
C
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Stremnitzer
Caroline
C
Mlitz
Veronika
V
Kezic
Sanja
S
Kammeyer
Arthur
A
Ghannadan
Minoo
M
Posa-Markaryan
Katja
K
Selden
Clare
C
Tschachler
Erwin
E
Eckhart
Leopold
L
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology; D004817:Epidermis / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects; D006638:Histidine Ammonia-Lyase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014560:Urocanic Acid / Q000378:metabolism*
D011740:Pyrimidine Dimers; D006638:Histidine Ammonia-Lyase; D014560:Urocanic Acid