Universität zu Köln

Lenz, Bernd ORCID: 0000-0001-6086-0924, Klafki, Hans-Wolfgang, Hillemacher, Thomas, Frieling, Helge ORCID: 0000-0001-5146-9720, Clepce, Marion, Gossler, Andrea, Thuerauf, Norbert, Winterer, Georg, Kornhuber, Johannes ORCID: 0000-0002-8096-3987 and Bleich, Stefan (2012). ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior. Addict. Biol., 17 (6). S. 1026 - 1036. HOBOKEN: WILEY-BLACKWELL. ISSN 1355-6215

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Abstract

From studies in cultured cells and animal models, nicotine and alcohol are known to regulate extracellular signal-regulated kinase 1 and 2 (ERK1/2). Alterations of ERK1/2 are thought to contribute to the drugs' rewarding effects. Accumulating evidence supports the importance of ERK1/2 in the molecular pathophysiology of depression and affective regulation in the hippocampus. We recently showed that the expression and phosphorylation of cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) in human buffy coat were associated with smoking behavior. Because ERK1/2 is known to effect phosphorylation of CREB, the aim of the present study was to further elucidate whether cigarette smoking leads to alterations in terms of ERK1/2 in human buffy coat as well. In a comparison of 53 smokers with 146 non-smoking controls, we found significantly higher levels of ERK1/2 protein (P = 0.004). In contrast, phospho-ERK1/2, phospho-/total-ERK1/2 ratio, mRNA-ERK1 and mRNA-ERK2 were not significantly different. Multiple regression analysis revealed a significant relation among the number of cigarettes smoked daily (R2 = 0.266, P = 0.003), the Fagerstrom Test for Nicotine Dependence score (R2 = 0.149, P = 0.032) and the mRNA expression of ERK1. Moreover, our analysis suggests that the mRNA expression of ERK2 might be linked to mood (model summary: R2 = 0.087, P = 0.019; mRNA-ERK2: P = 0.026). Given that the ERK1/2 signaling pathway plays an important role in the physiology and pathophysiology of affective and addictive behavior, our findings provide a rationale basis for additional mechanistic studies that may lead to the development of novel signaling pathway selective therapeutics in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lenz, Bernd UNSPECIFIED orcid.org/0000-0001-6086-0924 UNSPECIFIED Klafki, Hans-Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillemacher, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Frieling, Helge UNSPECIFIED orcid.org/0000-0001-5146-9720 UNSPECIFIED Clepce, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Gossler, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Thuerauf, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Winterer, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornhuber, Johannes UNSPECIFIED orcid.org/0000-0002-8096-3987 UNSPECIFIED Bleich, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480176
DOI:	10.1111/j.1369-1600.2010.00264.x
Journal or Publication Title:	Addict. Biol.
Volume:	17
Number:	6
Page Range:	S. 1026 - 1036
Date:	2012
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1355-6215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGNAL-REGULATED KINASE; NICOTINE-INDUCED PHOSPHORYLATION; DEPRESSIVE-LIKE BEHAVIOR; LONG-TERM POTENTIATION; FORCED SWIM STRESS; SYNAPTIC PLASTICITY; ANTIDEPRESSANT TREATMENT; ALPHA-SYNUCLEIN; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS Multiple languages Biochemistry & Molecular Biology; Substance Abuse Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48017