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ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior

Authors

  • Bernd Lenz,

    Corresponding author
    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
      Bernd Lenz, Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6-10, D-91054 Erlangen, Germany. E-mail: bernd.lenz@uk-erlangen.de
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  • Hans-Wolfgang Klafki,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Klinik für Psychiatrie und Psychotherapie, LVR-Klinikum Essen, Kliniken und Institut der Universität Duisburg-Essen, Germany
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  • Thomas Hillemacher,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Center of Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany
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  • Helge Frieling,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Center of Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany
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  • Marion Clepce,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
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  • Andrea Gossler,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
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  • Norbert Thuerauf,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
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  • Georg Winterer,

    1. Cologne Center for Genomics (CCG), University of Cologne, Germany
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  • Johannes Kornhuber,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
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  • Stefan Bleich

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Center of Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany
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Bernd Lenz, Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6-10, D-91054 Erlangen, Germany. E-mail: bernd.lenz@uk-erlangen.de

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 Fagerström 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.

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