Multiple cytochrome P450 isozymes in murine skin: induction of P450 1A, 2B, 2E, and 3A by dexamethasone.
Multiple cytochrome P450 isozymes in murine skin: induction of P450 1A, 2B, 2E, and 3A by dexamethasone.
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小鼠皮肤中的多种细胞色素 P450 同工酶：地塞米松诱导 P450 1A、2B、2E 和 3A。
DOI：
10.1111/1523-1747.ep12384210
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Mukhtar,H
中科院分区：
文献类型：
--
作者：
Jugert,FK;Agarwal,R;Kuhn,A;Bickers,DR;Merk,HF;Mukhtar,H
细胞色素P450（P450）是一个超基因家族的酶负责代谢的范围广泛的内源性和外源性化合物。P450同工酶具有重叠底物特异性。已知全身给予地塞米松（皮肤病学实践中广泛使用的局部药剂）可导致肝脏中多种P450同工酶的诱导。在这项研究中，局部应用地塞米松对小鼠皮肤中P450依赖性单加氧酶活性、P450同工酶表达和P450 mRNA水平的影响进行了评估。用地塞米松处理小鼠导致7-乙氧基试卤灵O-脱乙基酶（2.3倍）、7-戊氧基试卤灵O-脱戊基酶（19.2倍）、对硝基苯酚羟化酶（7.5倍）和红霉素N-脱甲基酶（2.2倍）活性的显著诱导;单加氧酶分别优先由P450同工酶1A 1、2B 1、2 E1和3A催化。皮肤微粒体的免疫印迹分析，采用针对纯化的P450 1A 1/2，2B 1/2，2 E1，和3A的抗体，表明地塞米松治疗的结果增加免疫反应性（1.8 - 13.9倍）。在免疫组化染色的皮肤与抗体对P4502 B1/2，局部应用地塞米松导致在对微粒体蛋白在基底层的表皮和毛囊细胞的反应性增加。虽然CYP 1A 1和CYP 2 E1的mRNA的组成型表达在小鼠皮肤中是明显的，但地塞米松处理后这些mRNA水平的任何变化都不明显。我们的研究结果表明，地塞米松对小鼠皮肤的应用导致诱导几个家族的P450同工酶，表明小鼠皮肤含有多种诱导型P450同工酶，能够参与广泛的外源性物质和内源性化合物的代谢。
Cytochrome P450s (P450s) are a supergene family of enzymes responsible for the metabolism of a wide range of endogenous and foreign compounds. P450 isozymes possess overlapping substrate specificity. Systemic administration of dexamethasone, a widely used topical agent in dermatologic practice, to animals is known to result in the induction of multiple P450 isozymes in liver. In this study the effect of topical application of dexamethasone to mice on P450-dependent monooxygenase activities, expression of P450 isozymes, and P450 mRNA levels in skin was assessed. The treatment of mice with dexamethasone resulted in significant induction of 7-ethoxyresorufin O-deethylase (2.3 times), 7-pentoxyresorufin O-depentylase (19.2 times), para-nitrophenol hydroxylase (7.5 times), and erythromycin N-demethylase (2.2 times) activities; the monooxygenases catalyzed preferentially by P450 isozymes 1A1, 2B1, 2E1, and 3A, respectively. Immunoblot analysis of cutaneous microsomes, employing antibodies directed against purified P450s 1A1/2, 2B1/2, 2E1, and 3A, showed that dexamethasone treatment results in an increased immunoreactivity (1.8 – 13.9 times). In immunohistochemical staining of skin with antibody against P4502B1/2, topical application of dexamethasone resulted in an increased reactivity towards microsomal protein in the suprabasal layer of the epidermis and with the cells of the hair follicles. Whereas constitutive expression of mRNAs for CYP1A1 and CYP2E1 was evident in murine skin, any change in the levels of these mRNAs following treatment with dexamethasone was not apparent. The results of our study indicate that the application of dexamethasone to murine skin results in the induction of several families of P450 isozymes, suggesting that murine skin contains multiple inducible P450 isozymes capable of participating in the metabolism of a wide range of xenobiotics and endogenous compounds.
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DOI：
10.1111/1523-1747.ep12874606
发表时间：
1990-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
M. Pham;J. Magdalou;G. Siest;M. Lenoir;B. Bernard;J. Jamoulle;B. Shroot
通讯作者：
M. Pham;J. Magdalou;G. Siest;M. Lenoir;B. Bernard;J. Jamoulle;B. Shroot
大鼠皮肤中苯并（a）芘代谢和环氧化物代谢酶活性与年龄相关的变化。
DOI：
--
发表时间：
1983
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Mukhtar,H;Bickers,DR
通讯作者：
Bickers,DR
表皮细胞色素 P-450：对新生大鼠局部应用 3-甲基胆蒽诱导的异构体的免疫化学特征。
DOI：
--
发表时间：
1989
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Khan,WA;Park,SS;Gelboin,HV;Bickers,DR;Mukhtar,H
通讯作者：
Mukhtar,H
影响因子：
4.1
作者：
NASH, T
通讯作者：
NASH, T
影响因子：
3.9
作者：
LUBET, RA;MAYER, RT;GUENGERICH, FP
通讯作者：
GUENGERICH, FP