Biomaterial Database

Cytochrome P450 expression in human keratinocytes: an aryl hydrocarbon receptor perspective. 2004

Hollie I Swanson

Department of Molecular and Biomedical Pharmacology, University of Kentucky Medical School, 800 Rose Street, Lexington, KY 40536, USA. hswan@uky.edu

The goal of this review is to stress the importance of the cytochrome P450 (CYP) superfamily that is expressed in human skin in the hope that it may stimulate further study in an intriguing topic that currently suffers from a relative dearth of information. Like the cells that line the respiratory and GI tracts [X. Ding, L.S. Kaminsky, Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts, Annu. Rev. Pharmacol. Toxicol. 43 (2003) 149-173] those present in human skin express a variety of CYPs that play important roles in xenobiotic, drug and steroid metabolism. In addition, a few CYPs, with potentially novel roles in metabolism and keratinocyte function, have recently been discovered that appear to be expressed in a keratinocyte-specific manner [L. Du, S.M. Hoffman, D.S. Keeney, Epidermal CYP2 family cytochromes P450, Toxicol. Appl. Pharmacol. 195 (2004) 278-287]. However, in preparing this review, it soon became apparent that in contrast to the progress made in understanding these events in the liver, relatively little is known in the human skin. Thus, while a number of tantalizing stories are beginning to emerge, they are far from complete. In this review, a brief synopsis of the structure of skin and methods of culturing keratinocytes will be presented. This will be followed by an overview of the various CYPs and their putative regulators that have been currently identified to be expressed in human keratinocytes. Then, a more detailed analysis of CYP regulation that involves the aryl hydrocarbon receptor (AHR) signaling pathway will be offered in the hope that it may serve as a paradigm for other CYP regulatory studies in the skin. Finally, several clinical implications that may arise due to altered regulation of CYPs will be considered.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012867	Skin	The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D015603	Keratinocytes	Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.	Keratinocyte
D016922	Cellular Senescence	Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.	Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D018336	Receptors, Aryl Hydrocarbon	Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.	AH Receptors,Aryl Hydrocarbon Receptors,Dioxin Receptors,Receptors, AH,Receptors, Dioxin,TCDD Receptors,AH Receptor,Aryl Hydrocarbon Receptor,Dioxin Receptor,Polyaromatic Hydrocarbon Receptor,Polyaromatic Hydrocarbon Receptors,Receptors, 2,3,7,8-Tetrachlorodibenzo-p-dioxin,Receptors, Polyaromatic Hydrocarbon,Receptors, TCDD,TCDD Receptor,Receptor, AH,Receptor, Aryl Hydrocarbon,Receptor, Dioxin,Receptor, Polyaromatic Hydrocarbon,Receptor, TCDD
D020133	Reverse Transcriptase Polymerase Chain Reaction	A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.	Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse