Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13

Minghui Ji, Yudong Zhang, Na Li, Chao Wang, Rong Xia, Zhan Zhang and Shou-Lin Wang
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Minghui Ji: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Yudong Zhang: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Na Li: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Chao Wang: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Rong Xia: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Zhan Zhang: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China
Shou-Lin Wang: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China

IJERPH, 2017, vol. 14, issue 10, 1-13

Abstract: Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the human respiratory system, has been reported to mediate the metabolism and toxicity of cigarette smoke. We previously found that nicotine inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its influence on other components of cigarette smoke remains unclear. The nicotine component of cigarette smoke extract (CSE) was separated, purified, and identified using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O). Cell viability and apoptosis by Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted on immortalized human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13) or vector (B-V), respectively. Interestingly, CSE and CSE-O were toxic to BEAS-2B cells whereas CSE-N showed less cytotoxicity. CSE-O was more toxic to B-2A13 cells than to B-V cells (IC 50 of 2.49% vs. 7.06%), which was flatted by 8-methoxypsoralen (8-MOP), a CYP inhibitor. CSE-O rather than CSE or CSE-N increased apoptosis of B-2A13 cells rather than B-V cells. Accordingly, compared to CSE-N and CSE, CSE-O significantly changed the expression of three pairs of pro- and anti-apoptotic proteins, Bcl-2 Associated X Protein/B cell lymphoma-2 (Bax/Bcl-2), Cleaved Poly (Adenosine Diphosphate-Ribose) Polymerase/Poly (Adenosine Diphosphate-Ribose) Polymerase (C-PARP/PARP), and C-caspase-3/caspase-3, in B-2A13 cells. In addition, recombination of CSE-N and CSE-O (CSE-O/N) showed similar cytotoxicity and apoptosis to the original CSE. These results demonstrate that the nicotine component decreases the metabolic activation of CYP2A13 to CSE and aids in understanding the critical role of CYP2A13 in human respiratory diseases caused by cigarette smoking.

Keywords: cigarette smoke extract; nicotine; cytochrome P450 2A13; cytotoxicity; BEAS-2B cells (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2017
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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