Nicotine induces chromatin changes and c-Jun up-regulation in HL-60 leukemia cells
Secteur Prévention, Institut Jean-Godinot, 1 Avenue Général Koënig, 51056 Reims Cedex, France. Oncology Reports
(Impact Factor: 2.3).
01/2006; 14(6):1553-8. DOI: 10.3892/or.14.6.1553
Although nicotine has been implicated as a potential factor in the pathogenesis of human cancer, its mechanisms of action regarding cancer development remain largely unknown. HL-60 cells were used to investigate the effects of a short-term treatment with nicotine at concentrations found in the blood of smokers. The findings show that nicotine induces chromatin decondensation, histone H3 acetylation and up-regulation of the c-Jun transcription factor mRNA. This increase is inhibited by mecamylamine, a nicotinic receptor antagonist, suggesting that nicotine alters cellular function directly via nicotinic acetylcholine receptors and may then play a role in cell physiology and tumor promotion.
Available from: Monica Lamas
- "In fact, it is now well established that as a consequence of cocaine/amphetamine, alcohol or nicotine exposure, changes in the pattern of histone acetylation/deacetylation can be detected in different brain areas, and some of these changes occur in a drug-specific manner   . Furthermore, the analysis of the temporal dynamics as well as the transient or permanent nature of these changes, and the characteristics of the brain areas where they occur have allowed to link these molecular events to processes such as development of tolerance to the drug  and withdrawal manifestations  , among others. "
[Show abstract] [Hide abstract]
ABSTRACT: Toluene is a volatile organic solvent with addictive potential that exhibits similarities in its physiological effects and modes of action to other addictive drugs. Despite its widespread abuse, the molecular mechanisms driving the response and adaptation of the organism to this drug are not fully understood. In recent years, different epigenetic mechanisms that modulate gene expression have been shown to be associated to cocaine, amphetamine and alcohol misuse-induced alterations in neuronal function. For example, it has been demonstrated that drug consumption induces variations in histone acetylation levels in brain reward regions and these play a relevant role on the abuse-associated behavioral plasticity. In order to decipher whether repeated toluene exposure could mediate epigenetic changes in the rat brain, we here analyzed the acetylation pattern of histones H3 and H4 in three brain areas that have been previously associated to substance abuse reward pathways: the Nucleus Accumbens (NAc), the Ventral Tegmental Area (VTA) and the Central Amygdala (CeA). Using immunofluorescence analysis of brain sections with specific antibodies that recognize the acetylated forms of histones H3 and H4, we demonstrate that chronic toluene inhalation differentially modifies histone H3 and H4 acetylation in the NAc and the VTA while no effect is observed in the CeA. Our results suggest that the activity of chromatin-modifying enzymes such as histone de-acetylases (HDACs) in certain brain areas are responsive to toluene inhalation and might be crucial mediators in the addictive response to toluene.
[Show abstract] [Hide abstract]
ABSTRACT: The mitochondrion is the organelle responsible for generation of most usable energy in a cell. It also plays an important role in a series of physiological processes such as apoptosis and proliferation. Although previous studies have demonstrated that nicotine modulates the morphology and function of mitochondria, the mechanism(s) underlying these effects is largely unknown. In this study, using a microarray consisting of 4793 clones derived from a mouse dopamine cDNA library, we profiled the gene expression patterns for six brain regions (amygdala, hippocampus, nucleus accumbens, prefrontal cortex, striatum and ventral tegmental area) of female Sprague-Dawley rats subjected to nicotine treatment for 7 days through osmotic minipump infusion. We identified a number of genes and pathways, including components of the electron transport system of mitochondria, such as cytochrome c oxidase subunit I (Mt-co1), Mt-co2, Mt-co3, cytochrome b (Mt-cyb), mitochondrial NADH dehydrogenase 4 (Mt-nd4), and Mt-nd6, that were significantly modulated by nicotine in multiple brain regions. Bioinformatics analysis provided evidence that Gene Ontology categories related to the electron transport system were overrepresented in each brain region. Finally, the results from the microarray analysis were verified by quantitative RT-PCR for four representative genes. Together, our findings imply that mitochondria are involved in neuronal adaptation to chronic nicotine exposure.
[Show abstract] [Hide abstract]
ABSTRACT: Lymphocytes are reported to express nicotinic acetylcholine receptors (nAChR). However, no data are available on the expression of these nAChR on activated lymphocyte relatively to resting lymphocytes. In this study, we examined nAChR subunits expression in PHA-stimulated versus un-stimulated lymphocytes, and four leukemic cell lines. Cell stimulation with nicotine triggered calcium responses only in some experiments conducted with PHA-stimulated lymphocytes. Likewise, only the Jurkat and HL-60 cell lines displayed calcium waves upon nicotine stimulation, whereas the Raji and CCRF-CEM did not. All responding cells displayed an active form of the nicotinic a-7 nAChR. Indeed, use of 2 different sets of primers for the corresponding mRNA showed that expression of the full-length a-7 subunit mRNA was only present in PHA-stimulated lymphocytes for which calcium waves had been evidenced. Microscopy analysis of lymphocytes structure showed a direct relationship between their size, their a-7 nAChR expression, and calcium release upon nicotine stimulation. Then, this relationship suggested that lymphocytes need a prime activation to express the a-7 nAChR, and therefore to release calcium in response to nicotine.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.