ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior.
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 (R(2)=0.266, P=0.003), the Fagerström Test for Nicotine Dependence score (R(2)=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: R(2)=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.
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany. bernd.lenz@uk-erlangen.de
Bernd
B
Lenz
Hans-Wolfgang
HW
Klafki
Thomas
T
Hillemacher
Helge
H
Frieling
Marion
M
Clepce
Andrea
A
Gossler
Norbert
N
Thuerauf
Georg
G
Winterer
Johannes
J
Kornhuber
Stefan
S
Bleich
D000328:Adult; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis*; D012044:Regression Analysis; D015398:Signal Transduction; D012907:Smoking / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3