Mechanism and tissue specificity of nicotine-mediated lung S-adenosylmethionine reduction

The Journal of Biological Chemistry
Camilo A MoncadaSalim Merali

Abstract

We previously reported that chronic nicotine infusion blocks development of Pneumocystis pneumonia. This discovery developed from our work demonstrating the inability of this fungal pathogen to synthesize the critical metabolic intermediate S-adenosylmethionine and work by others showing nicotine to cause lung-specific reduction of S-adenosylmethionine in guinea pigs. We had found nicotine infusion to cause increased lung ornithine decarboxylase activity (rate-controlling enzyme of polyamine synthesis) and hypothesized that S-adenosylmethionine reduction is driven by up-regulated polyamine biosynthesis. Here we report a critical test of our hypothesis; inhibition of ornithine decarboxylase blocks the effect of nicotine on lung S-adenosylmethionine. Further support is provided by metabolite analyses showing nicotine to cause a strong diversion of S-adenosylmethionine toward polyamine synthesis and away from methylation reactions; these shifts are reversed by inhibition of ornithine decarboxylase. Because the nicotine effect on Pneumocystis is so striking, we considered the possibility of tissue specificity. Using laser capture microdissection, we collected samples of lung alveolar regions (site of infection) and respiratory epit...Continue Reading

References

Aug 1, 1987·European Journal of Cancer & Clinical Oncology·Y HornL J Marton
Aug 1, 1988·Antimicrobial Agents and Chemotherapy·A B ClarksonC Rosenberg
Jul 1, 1995·Antimicrobial Agents and Chemotherapy·S MeraliA B Clarkson
Nov 1, 1994·Antimicrobial Agents and Chemotherapy·M Sarić, A B Clarkson
Jan 26, 1996·Journal of Chromatography. B, Biomedical Applications·S Merali, A B Clarkson
Apr 1, 1997·Chest·B MovsasC J Link
Jan 20, 2000·Antimicrobial Agents and Chemotherapy·S MeraliA B Clarkson
May 16, 2000·The Journal of Biological Chemistry·S MeraliA B Clarkson
Jul 15, 2004·The Journal of Biological Chemistry·Kristin KeeCarl W Porter
Jan 26, 2005·The Journal of Biological Chemistry·Mehboob ShivjiSalim Merali
Apr 23, 2005·Biochemical and Biophysical Research Communications·Kyuheun KimYang-Sook Chun
Feb 13, 2007·The Journal of Allergy and Clinical Immunology·Céline BergeronQutayba Hamid
Jan 8, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Michael J SkellySalim Merali

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Citations

Jun 7, 2011·American Journal of Respiratory Cell and Molecular Biology·Oscar Perez-LealSalim Merali
Apr 7, 2017·Scientific Reports·Jian-Guo LiDomenico Praticò
Nov 30, 2016·Aging Cell·Jian-Guo LiDomenico Praticò

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