Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation.
<h4>Background</h4>Postulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who...
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2009
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oai:doaj.org-article:560f48c518334ac7bb46feb320e0217d2021-11-25T06:27:54ZSmoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation.1932-620310.1371/journal.pone.0007959https://doaj.org/article/560f48c518334ac7bb46feb320e0217d2009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19956754/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Postulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who had stopped smoking for a mean of 13 years.<h4>Methodology/principal findings</h4>5-HT, monoamine oxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA)--the 5-HT/MAO catabolite--in plasma samples. Both platelet 5-HT and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non-significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Surprisingly, the platelet 5-HT content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme protein concentration found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B protein concentration, a study of the methylation of its gene promoter was undertaken in a small supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity.<h4>Conclusions/significance</h4>This is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health.Jean-Marie LaunayMuriel Del PinoGilles ChironiJacques CallebertKatell Peoc'hJean-Louis MégnienJacques MalletAlain SimonFrancine RenduPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 11, p e7959 (2009) |
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Medicine R Science Q Jean-Marie Launay Muriel Del Pino Gilles Chironi Jacques Callebert Katell Peoc'h Jean-Louis Mégnien Jacques Mallet Alain Simon Francine Rendu Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| description |
<h4>Background</h4>Postulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who had stopped smoking for a mean of 13 years.<h4>Methodology/principal findings</h4>5-HT, monoamine oxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA)--the 5-HT/MAO catabolite--in plasma samples. Both platelet 5-HT and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non-significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Surprisingly, the platelet 5-HT content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme protein concentration found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B protein concentration, a study of the methylation of its gene promoter was undertaken in a small supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity.<h4>Conclusions/significance</h4>This is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health. |
| format |
article |
| author |
Jean-Marie Launay Muriel Del Pino Gilles Chironi Jacques Callebert Katell Peoc'h Jean-Louis Mégnien Jacques Mallet Alain Simon Francine Rendu |
| author_facet |
Jean-Marie Launay Muriel Del Pino Gilles Chironi Jacques Callebert Katell Peoc'h Jean-Louis Mégnien Jacques Mallet Alain Simon Francine Rendu |
| author_sort |
Jean-Marie Launay |
| title |
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| title_short |
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| title_full |
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| title_fullStr |
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| title_full_unstemmed |
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| title_sort |
smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/560f48c518334ac7bb46feb320e0217d |
| work_keys_str_mv |
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| _version_ |
1718413681577951232 |