Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation.
Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation.
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DOI：
10.1371/journal.pone.0007959
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发表时间：
2009-11-23
期刊：
影响因子：
3.7
通讯作者：
Rendu F
中科院分区：
文献类型：
--
作者：
Launay JM;Del Pino M;Chironi G;Callebert J;Peoc'h K;Mégnien JL;Mallet J;Simon A;Rendu F
假设5-羟色胺（5-HT），从吸烟激活的血小板释放可能参与吸烟诱导的血管修饰，我们研究了一系列的115名男性分布为当前吸烟者（S），从不吸烟者（NS）和前吸烟者（FS）谁已经停止吸烟平均13年。测定血小板中5-HT、单胺氧化酶（MAO-B）的活性和含量，以及血浆样品中5-HT/MAO的分解产物5-羟基吲哚乙酸（5-HIAA）。血小板5-HT和血浆5-HIAA水平均与10年心血管疾病相对危险度相关（P<0.01），但在调整吸烟状况后，这些相关性变得不显著，强调了在计算心血管疾病危险度时考虑的决定性危险因素是吸烟。令人惊讶的是，血小板5-HT含量在S和NS中相似，但FS中较低，FS中的血浆5-HIAA水平平行较高。这是不可预见的，因为吸烟期间MAO-B活性受到抑制（P<0.00001）。然而，这与S和FS中发现的高于NS的酶蛋白浓度一致（P<0.001）。因此，似乎在吸烟期间的MAO抑制被更高的合成所补偿。为了研究MAO-B蛋白浓度的持续增加，在类似受试者的小补充队列中进行了其基因启动子甲基化的研究。我们发现，由于香烟烟雾诱导的核酸去甲基化酶活性的增加，S和FS与NS相比，MAOB基因启动子的甲基化频率显著降低（P<0.0001）。这是第一个报告，吸烟诱导表观遗传修饰。更好地了解表观基因组可能有助于进一步阐明烟草成瘾的生理病理学和新的治疗方法的发展。研究结果可能比心血管损伤产生更大的影响，因为单胺氧化酶依赖的5-羟色胺催化剂也与成瘾、癌症易感性、行为和心理健康有关。
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. 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. 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.
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影响因子：
5.6
作者：
Hillemacher, Thomas;Frieling, Helge;Linnebank, Michael
通讯作者：
Linnebank, Michael
影响因子：
4.7
作者：
CESURA, AM;GALVA, MD;DAPRADA, M
通讯作者：
DAPRADA, M
影响因子：
2.4
作者：
Georgiou, Elisavet;Valeri, Rozalia;Kouidou, Sofia
通讯作者：
Kouidou, Sofia
DOI：
10.1073/pnas.1833106100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Fowler, JS;Logan, J;Vaska, P
通讯作者：
Vaska, P
影响因子：
5
作者：
Leonard, S;Breese, C;Freedman, R
通讯作者：
Freedman, R