Du Liping, Hoffman Susan M G, Keeney Diane S
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Toxicol Appl Pharmacol. 2004 Mar 15;195(3):278-87. doi: 10.1016/j.taap.2003.09.020.
Skin is the largest and most accessible drug-metabolizing organ. In mammals, it is the competent barrier that protects against exposure to harmful stimuli in the environment and in the systemic circulation. Skin expresses many cytochromes P450 that have critical roles in exogenous and endogenous substrate metabolism. Here, we review evidence for epidermal expression of genes from the large CYP2 gene family, many of which are expressed preferentially in extrahepatic tissues or specifically in epithelia at the environmental interface. At least 13 CYP2 genes (CYP2A6, 2A7, 2B6, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 2R1, 2S1, 2U1, and 2W1) are expressed in skin from at least some human individuals, and the majority of these genes are expressed in epidermis or cultured keratinocytes. Where epidermal expression has been localized in situ by hybridization or immunocytochemistry, CYP2 transcripts and proteins are most often expressed in differentiated keratinocytes comprising the outer (suprabasal) cell layers of the epidermis and skin appendages. The tissue-specific transcriptional regulation of CYP2 genes in the epidermis, and in other epithelia that interface with the environment, suggests important roles for at least some CYP2 gene products in the production and disposition of molecules affecting competency of the epidermal barrier.
皮肤是最大且最易接触的药物代谢器官。在哺乳动物中，它是有效的屏障，可防止机体暴露于环境和体循环中的有害刺激物。皮肤表达许多细胞色素P450，这些细胞色素在内外源底物代谢中起关键作用。在此，我们综述了来自大型CYP2基因家族的基因在表皮表达的证据，其中许多基因优先在肝外组织表达或特异性地在与环境接触的上皮中表达。至少13个CYP2基因（CYP2A6、2A7、2B6、2C9、2C18、2C19、2D6、2E1、2J2、2R1、2S1、2U1和2W1）在至少部分人类个体的皮肤中表达，并且这些基因中的大多数在表皮或培养的角质形成细胞中表达。通过杂交或免疫细胞化学将表皮表达定位到原位时，CYP2转录本和蛋白质最常表达于构成表皮和皮肤附属器外层（基底层以上）细胞层的分化角质形成细胞中。表皮以及其他与环境接触的上皮中CYP2基因的组织特异性转录调控表明，至少某些CYP2基因产物在影响表皮屏障功能的分子的产生和处置中起重要作用。
