Kramer-Stickland K, Liebler D C
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson 85721, USA.
J Invest Dermatol. 1998 Aug;111(2):302-7. doi: 10.1046/j.1523-1747.1998.00273.x.
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.
我们评估了α-生育酚醋酸酯（α-TAc）在小鼠表皮及表皮匀浆上清液中水解为活性抗氧化剂α-生育酚（α-TH）的情况。局部应用α-TH可预防C3H小鼠的UVB光致癌作用，而α-TAc则不能。在用氘标记的α-TAc（d3-α-TAc）局部处理的小鼠中监测皮肤中的水解情况。从小鼠分离表皮样本，通过气相色谱-质谱法分析内源性（d0-α-TAc）和d3-α-TH。在24小时内，d3-α-TH的水平比内源性d0-α-TH水平增加了高达10倍；然而，在用d3-α-TAc之前接受UVB照射的小鼠中，d3-α-TH的水平比内源性d0-α-TH增加了高达30 - 40倍。α-TAc水解的这种增强随着UVB剂量的增加而增加。先前的UVB暴露可能通过增加表皮酯酶活性来增加α-TAc的水解。在未照射和照射小鼠的表皮2000 x g上清液中测量非特异性酯酶活性。非特异性酯酶底物α-萘酯在未照射小鼠的上清液中转化为α-萘酚。在照射小鼠的上清液中，水解为α-萘酚的量增加了约3倍。α-TAc水解为α-TH也发生在未照射小鼠的上清液中，并且在照射动物的上清液中这种水解增加了约3倍。这些数据表明，UVB可增加皮肤中的非特异性酯酶活性，α-TAc在含有非特异性酯酶的匀浆组分中转化为α-TH，并且UVB暴露可在体内调节α-TAc向α-TH的代谢。
