Epidermal CYP2 family cytochromes P450
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 sub...
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Published in | Toxicology and applied pharmacology Vol. 195; no. 3; pp. 278 - 287 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
15.03.2004
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Abstract | 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. |
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AbstractList | 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. |
Author | Du, Liping Keeney, Diane S Hoffman, Susan M G |
Author_xml | – sequence: 1 givenname: Liping surname: Du fullname: Du, Liping organization: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA – sequence: 2 givenname: Susan M G surname: Hoffman fullname: Hoffman, Susan M G – sequence: 3 givenname: Diane S surname: Keeney fullname: Keeney, Diane S |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15020190$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Animals Cytochrome P-450 Enzyme System - biosynthesis Cytochrome P-450 Enzyme System - genetics Gene Expression Regulation, Enzymologic Humans Skin - enzymology Transcription, Genetic |
Title | Epidermal CYP2 family cytochromes P450 |
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