title: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany. bernd.lenz@uk-erlangen.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Lenz
authors.forename: Hans-Wolfgang
authors.initials: HW
authors.lastname: Klafki
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.forename: Nils
authors.initials: N
authors.lastname: Killisch
authors.forename: Gerd
authors.initials: G
authors.lastname: Schaller
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.forename: Marion
authors.initials: M
authors.lastname: Clepce
authors.forename: Andrea
authors.initials: A
authors.lastname: Gossler
authors.forename: Norbert
authors.initials: N
authors.lastname: Thuerauf
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
mesh_terms: D000328:Adult; D000375:Aging / Q000097:blood; D000437:Alcoholism / Q000097:blood; D001007:Anxiety / Q000097:blood; D017362:Cyclic AMP Response Element-Binding Protein / Q000097:blood* / Q000235:genetics; D003863:Depression / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects*; D012727:Sex Characteristics; D012907:Smoking / Q000097:blood* / Q000235:genetics; D014029:Tobacco Use Disorder / Q000097:blood
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009538:Nicotine