Smoking behaviour is associated with expression and phosphorylation of CREB in human buffy coat

Abstract

Nicotine induces various acute und chronic pharmacological effects which can be long lasting and might lead to nicotine dependence. Nicotinic acetylcholine receptors (nAChRs) are involved in nicotine-induced phosphorylation of CREB (cyclic AMP response element-binding protein) in PC12h cells. Several studies, mainly done in animal models, report that CREB plays a role in anxiety, memory and substance abuse as well as in affective disorders. Information regarding nicotine effects on gene expression in humans in vivo is rare. The aim of our study was to determine whether or not there are differences between smokers and non-smoking controls in terms of CREB expression and phosphorylation in human buffy coat. Comparing 32 smokers with 76 non-smoking controls we found significantly elevated relative (p=0.043) and absolute (p=0.040) CREB phosphorylation in the blood of smokers who had smoked two cigarettes in the past 6 h. In contrast, the score of the State and Trait Anxiety Inventory, total-CREB and mRNA-CREB were not significantly different. Multiple regression analysis revealed a significant relation between the number of cigarettes smoked daily (R2=0.143, p=0.023), the Fagerström Test for Nicotine Dependence score (R2=0.145, p=0.022) and the expression of CREB. Moreover, in accord with previously published data our analysis suggests gender and age as factors that significantly influence expression and phosphorylation of CREB. It appears that human buffy coat is suitable for studying pharmacological effects of substances such as nicotine on selected signal transduction pathways in humans in vivo. This kind of study may be helpful for translating findings from animal models and cell cultures.

Effects of Carbocysteine and Beclomethasone on Histone Acetylation/Deacetylation Processes in Cigarette Smoke Exposed Bronchial Epithelial Cells

“…The increased expression of both p‐CREB and p300/CBP was related to a direct effect of cigarette smoke exposure as assessed here in an in vitro model of bronchial epithelial cells. In this regard, it was previously demonstrated that nicotine activated ERK 1/2 thus leading to increased activation of CREB in peripheral blood of smokers (Lenz et al, , ). Since TLR4 activation promotes CREB activation (Mellett et al, ) and since cigarette smoke activates TLR4 and induces ERK 1/2 activation (Pace et al, ), it is conceivable that cigarette smoke activates CREB via TLR4 and ERK 1/2 activation in bronchial epithelial cells.…”

NACP-Rep1 relates to Beck Depression Inventory Scores in Healthy Humans

“…Quantification of mRNA-SNCA mRNA was extracted from whole blood and reverse transcription was performed according to the manufacturer's instructions (RNeasy Mini Kit, Qiagen, Hilden, Germany; iScript cDNA Synthesis System, Bio-Rad, CA, USA) as previously described (Lenz et al 2010). Although DNase digestion is not required since RNeasy technology efficiently removes most of the DNA without DNAse treatment, we used the optional on-column DNase digestion with the RNase-free DNase Set (Qiagen, Hilden, Germany).…”

Diurnal variation in nicotine sensitivity in mice: Role of genetic background and melatonin

“…Nicotine has been shown to increase CREB activity in vitro and in vivo via several nAChR subtypes (Lenz et al 2010; Pluzarev and Pandey 2004; Hou et al 2004; Brunzell et al 2003; Hu et al 2002; Nakayama et al 2001) and activation of CREB seems to be essential for some behavioral responses to nicotine including conditioned place preference (Pascual et al 2009; Brunzell et al 2009). In contrast, melatonin signaling through Mtnr1a and/or Mtnr1b typically inhibits the protein kinase A signaling pathway, including reducing CREB activity via pertussis toxin sensitive G i proteins (Hardeland 2009).…”