Selective expression of CYP2A13 in human pancreatic α-islet cells

Yu Guo, Liang Ru Zhu, Gang Lu, Hui Wang, Jun Yan Hong

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1878-1882
Number of pages5
JournalDrug Metabolism and Disposition
Volume40
Issue number10
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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