Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma
Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. Howe...
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MDPI AG
2016-02-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/8/1/4 |
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| author | Venil N. Sumantran Pratik Mishra Rakesh Bera Natarajan Sudhakar |
| author_facet | Venil N. Sumantran Pratik Mishra Rakesh Bera Natarajan Sudhakar |
| author_sort | Venil N. Sumantran |
| collection | DOAJ |
| description | Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T12:36:56Z |
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| spelling | doaj.art-c65d7ca876784290a239530dfb3a718b2022-12-22T04:23:36ZengMDPI AGPharmaceutics1999-49232016-02-0181410.3390/pharmaceutics8010004pharmaceutics8010004Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and MelanomaVenil N. Sumantran0Pratik Mishra1Rakesh Bera2Natarajan Sudhakar3Department of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamil Nadu 600095, IndiaDepartment of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamil Nadu 600095, IndiaDepartment of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamil Nadu 600095, IndiaDepartment of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamil Nadu 600095, IndiaCytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene.http://www.mdpi.com/1999-4923/8/1/4psoriasismelanomamicroarrayCYP450drug metabolismpersonalized medicine |
| spellingShingle | Venil N. Sumantran Pratik Mishra Rakesh Bera Natarajan Sudhakar Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma Pharmaceutics psoriasis melanoma microarray CYP450 drug metabolism personalized medicine |
| title | Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma |
| title_full | Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma |
| title_fullStr | Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma |
| title_full_unstemmed | Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma |
| title_short | Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma |
| title_sort | microarray analysis of differentially expressed genes encoding cyp450 and phase ii drug metabolizing enzymes in psoriasis and melanoma |
| topic | psoriasis melanoma microarray CYP450 drug metabolism personalized medicine |
| url | http://www.mdpi.com/1999-4923/8/1/4 |
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