Effect of UVB on hydrolysis of alpha-tocopherol acetate to alpha-tocopherol in mouse skin.
We have assessed the hydrolysis of alpha-tocopherol acetate (alpha-TAc) to the active antioxidant alpha-tocopherol (alpha-TH) in mouse epidermis and in supernatant from epidermal homogenates. Topically administered alpha-TH prevents UVB photocarcinogenesis in C3H mice, whereas alpha-TAc does not. Hydrolysis in skin was monitored in mice treated topically with deuterium labeled alpha-TAc (d3-alpha-TAc). Epidermal samples were isolated from mice and analyzed for endogenous (d0-alpha-TAc) and d3-alpha-TH by gas chromatography-mass spectrometry. Within 24 h, the levels of d3-alpha-TH increased up to 10-fold over endogenous d0-alpha-TH levels; however, in mice irradiated with UVB prior to the application of d3-alpha-TAc, levels of d3-alpha-TH increased up to 30-40-fold over endogenous d0-alpha-TH. This enhancement of alpha-TAc hydrolysis increased with increasing UVB dose. Prior UVB exposure may increase hydrolysis of alpha-TAc by increasing epidermal esterase activity. Nonspecific esterase activity was measured in the 2000 x g supernatant from epidermis of unirradiated and irradiated mice. Alpha-napthyl acetate, a nonspecific esterase substrate, was converted to alpha-napthol in supernatants from unirradiated mice. Hydrolysis to alpha-napthol increased approximately 3-fold in supernatants from irradiated mice. Hydrolysis of alpha-TAc to alpha-TH also occurred in supernatant from unirradiated mice, and this hydrolysis increased approximately 3-fold in supernatant from irradiated animals. These data indicate that nonspecific esterase activity was increased by UVB in the skin, that alpha-TAc is converted to alpha-TH in the homogenate fraction containing nonspecific esterase, and that UVB exposure modulates the metabolism of alpha-TAc to alpha-TH in vivo.
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson 85721, USA.
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Kramer-Stickland
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Liebler
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D051379:Mice; D008809:Mice, Inbred C3H; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D024505:Tocopherols; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D000975:Antioxidants; D014810:Vitamin E; D010751:Phosphopyruvate Hydratase; D024502:alpha-Tocopherol; D024505:Tocopherols