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Rapid CommunicationShort Communication

Selective Expression of CYP2A13 in Human Pancreatic α-Islet Cells

Yu Guo, Liang-Ru Zhu, Gang Lu, Hui Wang and Jun-Yan Hong
Drug Metabolism and Disposition October 2012, 40 (10) 1878-1882; DOI: https://doi.org/10.1124/dmd.112.046359
Yu Guo
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China (Y.G., H.W.); School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey (Y.G., J.-Y.H.); Union Hospital, Tongji Medical College, Huazhong Science & Technology University, Wuhan, China (L.-R.Z.); and Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey (G.L.)
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Liang-Ru Zhu
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China (Y.G., H.W.); School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey (Y.G., J.-Y.H.); Union Hospital, Tongji Medical College, Huazhong Science & Technology University, Wuhan, China (L.-R.Z.); and Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey (G.L.)
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Gang Lu
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China (Y.G., H.W.); School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey (Y.G., J.-Y.H.); Union Hospital, Tongji Medical College, Huazhong Science & Technology University, Wuhan, China (L.-R.Z.); and Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey (G.L.)
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Hui Wang
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China (Y.G., H.W.); School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey (Y.G., J.-Y.H.); Union Hospital, Tongji Medical College, Huazhong Science & Technology University, Wuhan, China (L.-R.Z.); and Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey (G.L.)
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Jun-Yan Hong
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China (Y.G., H.W.); School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey (Y.G., J.-Y.H.); Union Hospital, Tongji Medical College, Huazhong Science & Technology University, Wuhan, China (L.-R.Z.); and Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey (G.L.)
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Abstract

Exposure to cigarette smoke is an etiological factor of human pancreatic cancer and has been associated with an increased risk of pancreatic diseases, including pancreatitis and diabetes. The toxicants in cigarette smoke can reach pancreatic tissue, and most of the toxicants require cytochrome P450 (P450)-mediated metabolic activation to exert their toxicity. Among all the human P450 enzymes, CYP2A13 is the most efficient enzyme in the metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major tobacco-specific toxicant and a suspected human carcinogen. It also metabolically activates 4-aminobiphenyl, another toxicant in cigarette smoke. Immunohistochemical analysis in this study demonstrated that CYP2A13 was selectively expressed in the islets but not in the exocrine portion of adult human pancreas. Further study using dual immunofluorescence labeling technique showed that CYP2A13 protein was mainly expressed in the α-islet but not in β-islet cells. The selective expression of CYP2A13 in human pancreatic α-islet cells suggests that these islet cells could be damaged by the toxicants existing in cigarette smoke through CYP2A13-mediated in situ metabolic activation. Our result provides a mechanistic insight for human pancreatic diseases that have been associated with cigarette smoke exposure.

Footnotes

  • This work was supported in part by the National Institutes of Health National Institute of Environmental Health Sciences [Grant R01-ES10048] (to J.-Y.H.); and The Flight Attendant Medical Research Institute [Grant CIA-082500] (to J.-Y.H.).

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    http://dx.doi.org/10.1124/dmd.112.046359.

  • ABBREVIATIONS:

    NNK
    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
    P450
    cytochrome P450
    FITC
    fluorescein isothiocyanate
    POR
    P450 oxidoreductase.

  • Received May 1, 2012.
  • Accepted July 13, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 40 (10)
Drug Metabolism and Disposition
Vol. 40, Issue 10
1 Oct 2012
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Rapid CommunicationShort Communication

CYP2A13 EXPRESSION IN HUMAN PANCREATIC ISLETS

Yu Guo, Liang-Ru Zhu, Gang Lu, Hui Wang and Jun-Yan Hong
Drug Metabolism and Disposition October 1, 2012, 40 (10) 1878-1882; DOI: https://doi.org/10.1124/dmd.112.046359

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Rapid CommunicationShort Communication

CYP2A13 EXPRESSION IN HUMAN PANCREATIC ISLETS

Yu Guo, Liang-Ru Zhu, Gang Lu, Hui Wang and Jun-Yan Hong
Drug Metabolism and Disposition October 1, 2012, 40 (10) 1878-1882; DOI: https://doi.org/10.1124/dmd.112.046359
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