title: Nicotine mediates hypochlorous acid-induced nuclear protein damage in mammalian cells.
abstract: Activated neutrophils secrete hypochlorous acid (HOCl) into the extracellular space of inflamed tissues. Because of short diffusion distance in biological fluids, HOCl-damaging effect is restricted to the extracellular compartment. The current study aimed at investigating the ability of nicotine, a component of tobacco and electronic cigarettes, to mediate HOCl-induced intracellular damage. We report, for the first time, that HOCl reacts with nicotine to produce nicotine chloramine (Nic-Cl). Nic-Cl caused dose-dependent damage to proliferating cell nuclear antigen (PCNA), a nuclear protein, in cultured mammalian lung and kidney cells. Vitamin C, vitamin E analogue (Trolox), glutathione, and N-acetyl-L-cysteine inhibited the Nic-Cl-induced PCNA damage, implicating oxidation in PCNA damage. These findings point out the ability of nicotine to mediate HOCl-induced intracellular damage and suggest antioxidants as protective measures. The results also raise the possibility that Nic-Cl can be created in the inflamed tissues of tobacco and electronic cigarette smokers and may contribute to smoking-related diseases.
authors.affiliation: Division of Biochemistry and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Kingdom of Saudi Arabia, salama.3@buckeyemail.osu.edu.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Salama
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Maghrabi
authors.forename: Robert M
authors.initials: RM
authors.lastname: Snapka
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry*; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D009538:Nicotine / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D002839:Chromans; D018809:Proliferating Cell Nuclear Antigen; D009538:Nicotine; D006997:Hypochlorous Acid; D005978:Glutathione; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine