Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival

• Published in: Experimental dermatology 2009-07, Vol.18 (7), p.611-618
• Main Authors: Marín, Yarí E., Seiberg, Miri, Lin, Connie B.
• Format: Article
• Language: English
• Subjects: 20-Hydroxysteroid Dehydrogenases - genetics; 20-Hydroxysteroid Dehydrogenases - metabolism; 3-Hydroxysteroid Dehydrogenases - genetics; 3-Hydroxysteroid Dehydrogenases - metabolism; AKR1C1; aldo-keto reductase; Aldo-Keto Reductase Family 1 Member C3; Animals; Apoptosis - radiation effects; Biological and medical sciences; Cell Survival - radiation effects; Cells, Cultured; Dermatology; Dose-Response Relationship, Radiation; Gene Expression Regulation - radiation effects; Humans; Hydroxyprostaglandin Dehydrogenases - genetics; Hydroxyprostaglandin Dehydrogenases - metabolism; Hydroxysteroid Dehydrogenases - genetics; Hydroxysteroid Dehydrogenases - metabolism; keratinocytes; Keratinocytes - cytology; Keratinocytes - metabolism; Keratinocytes - radiation effects; Medical sciences; reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; Skin - cytology; Skin - metabolism; Skin - radiation effects; Swine; Ultraviolet Rays; UVB
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2008.00839.x

:  Human skin is endowed with the capacity to synthesize and metabolize steroid hormones, a function of importance in skin physiology and pathology. It is the hormone‐regulatory enzymes, including the aldo‐keto reductase 1C subfamily (AKR1Cs) that are largely responsible for the local levels of active steroid hormones. AKR1C1 and AKR1C2 inactivate progesterone and 5α‐dihydrotestosterone, respectively, whereas AKR1C3 activates oestradiol and testosterone. Here, we show that AKR1C1‐3 are expressed in keratinocytes and fibroblasts, with marginal expression in melanocytes. In human primary keratinocytes, AKR1C1 and ‐2 were UVB‐inducible in a dose‐dependent manner, as shown by quantitative PCR and Western blot analyses. The induction of AKR1C1 by UVB was concomitant with the presence of an apoptotic marker, the cleavage product of poly‐ADP ribose polymerase. Similarly, the activation of AKR1C1 and ‐2 upon UVB exposure was demonstrated in swine skin in vivo and in human skin explants. As expected, hydrogen peroxide‐derived reactive oxygen species also induced AKR1C1 and ‐2 mRNA and protein levels in keratinocytes in a dose‐dependent manner. Furthermore, down‐regulation of AKR1Cs by small interfering ribonucleic acid led to significantly reduced cell viability. Based on the combined evidence of the presence of an apoptotic marker in the UVB‐exposed keratinocytes with increased AKR1Cs expression and reduced cell viability in down‐regulated AKR1Cs, we suggest that AKR1C subfamily genes are stress‐inducible and might function as survival factors in keratinocytes.