title: Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants.
abstract: Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and beta-naphthylamine (beta-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H(2)O(2) or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.
authors.affiliation: Univ Paris Diderot-Paris 7, Unit of Functional and Adaptative Biology (BFA) affiliated with CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.forename: Emile
authors.initials: E
authors.lastname: Petit
authors.forename: Nilusha
authors.initials: N
authors.lastname: Ragunathan
authors.forename: Armelle
authors.initials: A
authors.lastname: Baeza-Squiban
authors.forename: Francelyne
authors.initials: F
authors.lastname: Marano
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Dupret
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues-Lima
mesh_terms: D015081:2-Naphthylamine / Q000493:pharmacokinetics; D000107:Acetylation; D000611:Aminobiphenyl Compounds / Q000493:pharmacokinetics; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001711:Biotransformation; D001980:Bronchi / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000494:pharmacology
chemical_list: D000611:Aminobiphenyl Compounds; D016877:Oxidants; D030421:Peroxynitrous Acid; C006757:4-biphenylamine; D006861:Hydrogen Peroxide; D015081:2-Naphthylamine; D001191:Arylamine N-Acetyltransferase