Effects of the differentiated keratinocyte phenotype on expression levels of CYP1–4 family genes in human skin cells
Autor: | Patricia A. Ladd, Garold S. Yost, Liping Du, Diane S. Keeney, Diane L. Lanza, Mark M. Neis |
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Rok vydání: | 2006 |
Předmět: |
Keratinocytes
Male Epoxygenase Cellular differentiation Cell Culture Techniques Human skin Toxicology Epoxyeicosatrienoic acid Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System medicine Humans RNA Messenger Pharmacology integumentary system Epidermis (botany) biology Cell Differentiation Monooxygenase Up-Regulation Cell biology Isoenzymes Phenotype medicine.anatomical_structure Epidermal Cells Biochemistry chemistry CYP2S1 biology.protein Eicosanoids Epidermis Keratinocyte |
Zdroj: | Toxicology and Applied Pharmacology. 213:135-144 |
ISSN: | 0041-008X |
Popis: | Epoxyeicosatrienoic acids produced by mouse CYP2B19 have been implicated in mechanisms regulating epidermal cornification (Ladd, P.A., Du, L., Capdevila, J.H., Mernaugh, R., Keeney, D.S., 2003. Epoxyeicosatrienoic acids activate transglutaminases in situ and induce cornification of epidermal keratinocytes. J. Biol. Chem. 278, 35184-35192). In this study, we aimed to identify CYPs that are up-regulated during keratinocyte differentiation and potentially responsible for epoxyeicosatrienoic acid formation in human skin. The cellular differentiation state of human epidermal cell cultures was manipulated to resemble the basal, spinous, and granular cell phenotypes in vivo. Changes in CYP mRNA levels were measured as a function of differentiation state for a panel of 15 CYPs that included known and putative arachidonate monooxygenases. Quantitative real-time PCR analyses showed that all of the CYPs were expressed in differentiating epidermal cell cultures and in human epidermis, with the exception of CYP2B6, which was poorly expressed in vitro. Six CYPs were strongly up-regulated at Day 6 and Day 8 of in vitro differentiation (CYP4B1, 2W1, 2C18, 3A4, 2C19, 2C9); the increase in mRNA levels ranged from 27- to 356-fold. Only CYP2U1 mRNA levels decreased (6-fold change) during cellular differentiation. Six CYPs showed little variation ( |
Databáze: | OpenAIRE |
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