Browsing by Subject "nicotine"
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Item Open Access Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells(2004) Konu Ö.; Xu X.; Ma J.Z.; Kane J.; Wang J.; Shi, S.J.; Li, M.D.Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974±0.017 to 0.995±0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca2+]i) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress. © 2003 Elsevier B.V. All rights reserved.Item Open Access Investigation of the effects of nicotine and levamisole on SW620 colon adenocarcinoma cells using a customized r-routine for automated microarray analysis(2010) Üçal, MuammerNicotine, the addictive component of tobacco, shows proliferative and antiapoptotic activity in cancer cells. Levamisole, an antihelmintic, on the other hand, has been tested as an additive chemotherapeutic agent and in treatment of nephrotic syndrome. Nicotine and levamisole are both agonists of nicotinic acetylcholine receptors; effects of these two agents have not been studied in colon cancer transcriptome. In this study, nicotine and levamisole exposed SW620 colon cancer cells, at a dose of 1 μM for 7 days, were studied with respect to changes in expression using microarrays. For data analysis, a custom R-routine which makes extensive use of open source R-BioConductor Project and associated packages has been written; and it is composed of three modules: QualCont module performs quality controls supported with several visualItem Open Access A role for LYNX2 in anxiety-related behavior(2009) Tekinay, A.B.; Nong, Y.; Miwa J.M.; Lieberam I.; Ibanez-Tallon I.; Greengard P.; Heintz, N.Anxiety disorders are the most prevalent mental disorders in developed societies. Although roles for the prefrontal cortex, amygdala, hippocampus and mediodorsal thalamus in anxiety disorders are well documented, molecular mechanisms contributing to the functions of these structures are poorly understood. Here we report that deletion of Lynx2, a mammalian prototoxin gene that is expressed at high levels in anxiety associated brain areas, results in elevated anxiety-like behaviors. We show that LYNX2 can bind to and modulate neuronal nicotinic receptors, and that loss of Lynx2 alters the actions of nicotine on glutamatergic signaling in the prefrontal cortex. Our data identify Lynx2 as an important component of the molecular mechanisms that control anxiety, and suggest that altered glutamatergic signaling in the prefrontal cortex of Lynx2 mutant mice contributes to increased anxiety-related behaviors.