Serum-responsive expression of carbonyl-metabolizing enzymes in normal and transformed human buccal keratinocytes

Abstract.Gene expression of carbonyl-metabolizing enzymes (CMEs) was investigated in normal buccal keratinocytes (NBK) and the transformed buccal keratinocyte lines SVpgC2a and SqCC/Y1. Studies were performed at a serum concentration known to induce terminal squamous differentiation (TSD) in normal cells. Overall, 39 of 58 evaluated CMEs were found to be expressed at the transcript level. Together the transformed cell lines showed altered transcription of eight CME genes compared to NBK, substantiating earlier results. Serum increased transcript levels of ALDH1A3, DHRS3, HPGD and AKR1A1, and decreased those of ALDH4A1 in NBK; of these, the transformed, TSD-deficient cell lines partly retained regulation of ALDH1A3 and DHRS3. Activity measurements in crude cell lysates, including relevant enzymatic inhibitors, indicated significant capacity for CME-mediated xenobiotic metabolism among the cell lines, notably with an increase in serum-differentiated NBK. The results constitute the first evidence for differential CME gene expression and activity in non-differentiated and differentiated states of epithelial cells.

[1]  E. Fuchs,et al.  Regulation of terminal differentiation of cultured human keratinocytes by vitamin A , 1981, Cell.

[2]  M. Reiss,et al.  Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines. , 1992, Oncology research.

[3]  A. Hara,et al.  Multiplicity of mammalian reductases for xenobiotic carbonyl compounds. , 2006, Drug metabolism and pharmacokinetics.

[4]  E. Cadenas,et al.  DT-diaphorase: purification, properties, and function. , 1990, Methods in enzymology.

[5]  V. Vasiliou,et al.  Human aldehyde dehydrogenase 3A1 (ALDH3A1): biochemical characterization and immunohistochemical localization in the cornea. , 2003, The Biochemical journal.

[6]  J. Lutterbaugh,et al.  15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Eckert,et al.  Epidermal keratinocytes - genes and their regulation. , 1996, Cell death and differentiation.

[8]  B. Persson,et al.  Role of type-1 11beta-hydroxysteroid dehydrogenase in detoxification processes. , 1997, European journal of biochemistry.

[9]  R. Presland,et al.  Epithelial structural proteins of the skin and oral cavity: function in health and disease. , 2000, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[10]  E. Cadenas,et al.  [30] DT-diaphorase : purification, properties, and function , 1990 .

[11]  R. Grafström,et al.  Multiple genotypic aberrances associate to terminal differentiation-deficiency of an oral squamous cell carcinoma in serum-free culture. , 2008, Differentiation; research in biological diversity.

[12]  N. K. Ahmed,et al.  Comparison and characterization of mammalian xenobiotic ketone reductases. , 1979, The Journal of pharmacology and experimental therapeutics.

[13]  P. Kador,et al.  Inhibition of aldehyde reductase by aldose reductase inhibitors. , 1990, Biochemical pharmacology.

[14]  J. Farrés,et al.  Human and yeast zeta-crystallins bind AU-rich elements in RNA. , 2007, Cellular and molecular life sciences : CMLS.

[15]  A. Shojaei.  Buccal mucosa as a route for systemic drug delivery: a review. , 1998, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[16]  O. Barski,et al.  Regulation of aldehyde reductase expression by STAF and CHOP. , 2004, Genomics.

[17]  S Lippens,et al.  Death penalty for keratinocytes: apoptosis versus cornification , 2005, Cell Death and Differentiation.

[18]  L. Amzel,et al.  Structure and mechanism of NAD[P]H:quinone acceptor oxidoreductases (NQO). , 2004, Methods in enzymology.

[19]  H. Jörnvall,et al.  Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. , 1990, Biochemistry.

[20]  M. Sporn,et al.  Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C A Squier,et al.  Biology of oral mucosa and esophagus. , 2001, Journal of the National Cancer Institute. Monographs.

[22]  Taro Yamada,et al.  Crystal structure of human prostaglandin F synthase (AKR1C3). , 2004, Biochemistry.

[23]  F. Oesch,et al.  Carbonyl reductase provides the enzymatic basis of quinone detoxication in man. , 1986, Biochemical pharmacology.

[24]  R. Grafström,et al.  Micro-array chip analysis of carbonyl-metabolising enzymes in normal, immortalised and malignant human oral keratinocytes , 2001, Cellular and Molecular Life Sciences CMLS.

[25]  Roland C Grafström,et al.  The Application of Normal, SV40 T-antigen-immortalised and Tumour-derived Oral Keratinocytes, under Serum-free Conditions, to the Study of the Probability of Cancer Progression as a Result of Environmental Exposure to Chemicals , 2007, Alternatives to laboratory animals : ATLA.

[26]  P. Khavari,et al.  Control of Keratinocyte Proliferation and Differentiation by p63 , 2007, Cell cycle.

[27]  E. Anggard,et al.  Biosynthesis of prostaglandins from arachidonic acid in guinea pig lung. Prostaglandins and related factors. 38. , 1965, The Journal of biological chemistry.

[28]  U. Oppermann.  Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology. , 2007, Annual review of pharmacology and toxicology.

[29]  C. Betsholtz,et al.  Characterization of human buccal epithelial cells transfected with the simian virus 40 T-antigen gene. , 1995, Carcinogenesis.

[30]  D. Ong,et al.  Retinoic acid biosynthesis by normal human breast epithelium is via aldehyde dehydrogenase 6, absent in MCF-7 cells. , 2001, Cancer research.

[31]  Zsolt Sarang,et al.  Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes , 2002, International journal of cancer.

[32]  R. Grafström,et al.  Serum-free growth and karyotype analyses of cultured normal and tumorous (SqCC/Y1) human buccal epithelial cells. , 1991, Cancer communications.

[33]  A. Atalla,et al.  Purification and characterization of oxidoreductases-catalyzing carbonyl reduction of the tobacco-specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human liver cytosol , 2000, Xenobiotica; the fate of foreign compounds in biological systems.

[34]  Yusuke Nakamura,et al.  Identification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses , 2004, Journal of Human Genetics.

[35]  J V Castell,et al.  Cell lines: a tool for in vitro drug metabolism studies. , 2008, Current drug metabolism.

[36]  U. Oppermann,et al.  Molecular and structural aspects of xenobiotic carbonyl metabolizing enzymes. Role of reductases and dehydrogenases in xenobiotic phase I reactions. , 2000, Toxicology.

[37]  Roland C. Grafström,et al.  Alcohol dehydrogenase 3 transcription associates with proliferation of human oral keratinocytes , 2004, Cellular and Molecular Life Sciences CMLS.

[38]  T. Penning,et al.  Retention of NADPH-linked quinone reductase activity in an aldo-keto reductase following mutation of the catalytic tyrosine. , 1998, Biochemistry.

[39]  B. Wermuth.  Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. , 1981, The Journal of biological chemistry.

[40]  J. Zigler,et al.  Identification and characterization of the enzymatic activity of zeta-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase. , 1992, The Journal of biological chemistry.

[41]  A. Pfeifer,et al.  Cytochrome P450 expression and related metabolism in human buccal mucosa. , 2001, Carcinogenesis.

[42]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  R. Elling,et al.  Identification of a novel NADH-specific aldo-keto reductase using sequence and structural homologies. , 2006, The Biochemical journal.

[44]  J. Jarabak.  Polycyclic aromatic hydrocarbon quinones may be either substrates for or irreversible inhibitors of the human placental NAD-linked 15-hydroxyprostaglandin dehydrogenase. , 1992, Archives of biochemistry and biophysics.

[45]  T. Penning,et al.  Purification and properties of a 3α-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs , 1984 .

[46]  E. Maser,et al.  Carbonyl Reductases and Pluripotent Hydroxysteroid Dehydrogenases of the Short-chain Dehydrogenase/reductase Superfamily , 2007, Drug metabolism reviews.

[47]  R. Grafström,et al.  Growth regulation of serum-free cultures of epithelial cells from normal human buccal mucosa , 1991, In Vitro Cellular & Developmental Biology - Animal.

[48]  R. Grafström.  Human Oral Epithelium , 2002 .

[49]  A I Saeed,et al.  TM4: a free, open-source system for microarray data management and analysis. , 2003, BioTechniques.

[50]  R. Pietruszko,et al.  Purification and characterization of human liver "high Km" aldehyde dehydrogenase and its identification as glutamic gamma-semialdehyde dehydrogenase. , 1986, The Journal of biological chemistry.

[51]  L. Ernster,et al.  DT diaphorase. I. Purification from the soluble fraction of rat-liver cytoplasm, and properties. , 1962, Biochimica et biophysica acta.

[52]  J. Habener,et al.  Transcription Factors C/EBPα, C/EBPβ, and CHOP (Gadd153) Expressed During the Differentiation Program of Keratinocytes In Vitro and In Vivo , 1998 .

[53]  H. Tai,et al.  15-hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer. , 2007, Prostaglandins & other lipid mediators.

[54]  W. Pw,et al.  Cellular and molecular basis of barrier function in oral epithelium. , 1991 .

[55]  Yi Jin,et al.  Aldo-keto reductases and bioactivation/detoxication. , 2007, Annual review of pharmacology and toxicology.

[56]  I. Screpanti,et al.  retSDR1, a short-chain retinol dehydrogenase/reductase, is retinoic acid-inducible and frequently deleted in human neuroblastoma cell lines. , 2002, Cancer research.

[57]  Roland C Grafström,et al.  Bioinformatics processing of protein and transcript profiles of normal and transformed cell lines indicates functional impairment of transcriptional regulators in buccal carcinoma. , 2007, Journal of proteome research.

[58]  D. Harrison,et al.  Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. , 1999, The Biochemical journal.

[59]  Y. Urade,et al.  Enzymatic conversion of prostaglandin H2 to prostaglandin F2 alpha by aldehyde reductase from human liver: comparison to the prostaglandin F synthetase from bovine lung. , 1989, The Journal of biological chemistry.

[60]  P. Sacks.  Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck , 1996, Cancer and Metastasis Reviews.

[61]  D. Gustafson,et al.  Enhancement of xanthine dehydrogenase mediated mitomycin C metabolism by dicumarol. , 1992, Cancer research.