Bickers D R, Mukhtar H, Dutta-Choudhury T, Marcelo C L, Voorhees J J
J Invest Dermatol. 1984 Jul;83(1):51-6. doi: 10.1111/1523-1747.ep12261680.
Prior studies have shown that human skin possesses a cytochrome P-450-dependent microsomal enzyme that is capable of metabolizing drugs and polycyclic aromatic hydrocarbon (PAH) carcinogens. This study characterized benzo[a]pyrene (BP) metabolism in human epidermis of normal and psoriatic individuals. The basal level of the cytochrome P-450-dependent microsomal enzyme aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) were measured in freshly keratomed epidermis from 12 normal individuals and from uninvolved skin sites of 12 patients with psoriasis. The induction response of AHH following the in vitro addition of the PAH benz[a]anthracene (BA) was also assessed. The basal activity (mean +/- SE) of AHH in normal epidermis was 62.1 +/- 5.6 units (fmol 3-hydroxybenzo[a]pyrene, 3-OH-BP/min/mg protein) whereas the activity in uninvolved skin of psoriatic individuals was 62.9 +/- 5.1 units (NS), Epoxide hydrolase activity was 25.1 +/- 1.1 (pmol BP 4,5-diol/min/mg protein) unites in normal epidermis and 24.8 +/- 2.1 units in epidermis from patients with psoriasis (NS). Following addition of BA (100 microM), in vitro, AHH activity in normal epidermis increased by a mean value of 165% whereas activity in nonlesional epidermis of psoriatic individuals increased 320%. Kinetic studies in normal epidermis revealed that AHH reaction was linear up to 60 min and to 50 micrograms protein, had a pH optimum of 7.4, and the Km for BP was 0.62 microM. High-performance liquid chromatography (HPLC) confirmed that the pattern of metabolism of BP was quite similar in epidermal microsomes prepared from normal and psoriatic individuals, insofar as the formation of diols, phenols, and quinones was concerned. These studies indicate that human epidermis is capable of metabolizing BP and that there is no significant difference between normal individuals and patients with psoriasis insofar as basal AHH activity or total BP metabolism is concerned. Furthermore, the epidermal enzyme system in patients with psoriasis has a greater responsiveness to environmental PAH than does that of normal individuals.
先前的研究表明，人类皮肤拥有一种细胞色素P - 450依赖的微粒体酶，它能够代谢药物和多环芳烃（PAH）致癌物。本研究对正常个体和银屑病患者的人类表皮中苯并[a]芘（BP）的代谢进行了表征。在12名正常个体的新鲜角膜切开表皮以及12名银屑病患者未受累皮肤部位测量了细胞色素P - 450依赖的微粒体酶芳烃羟化酶（AHH）和环氧化物水解酶（EH）的基础水平。还评估了体外添加PAH苯并[a]蒽（BA）后AHH的诱导反应。正常表皮中AHH的基础活性（平均值±标准误）为62.1±5.6单位（fmol 3 - 羟基苯并[a]芘，3 - OH - BP/分钟/毫克蛋白质），而银屑病个体未受累皮肤中的活性为62.9±5.1单位（无显著性差异），环氧化物水解酶活性在正常表皮中为25.1±1.1（pmol BP 4,5 - 二醇/分钟/毫克蛋白质）单位，在银屑病患者的表皮中为24.8±2.1单位（无显著性差异）。体外添加BA（100μM）后，正常表皮中AHH活性平均增加了165%，而银屑病个体非皮损表皮中的活性增加了320%。对正常表皮的动力学研究表明，AHH反应在长达60分钟和50微克蛋白质时呈线性，最适pH为7.4，BP的Km为0.62μM。高效液相色谱（HPLC）证实，就二醇、酚和醌的形成而言，从正常个体和银屑病个体制备的表皮微粒体中BP的代谢模式非常相似。这些研究表明，人类表皮能够代谢BP，就基础AHH活性或总BP代谢而言，正常个体和银屑病患者之间没有显著差异。此外，银屑病患者的表皮酶系统对环境PAH的反应性比正常个体更强。
