ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior.
Addict Biol
; 17(6): 1026-35, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-21070506
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 (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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tabagismo
/
RNA Mensageiro
/
Fumar
/
Proteína Quinase 1 Ativada por Mitógeno
/
Proteína Quinase 3 Ativada por Mitógeno
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article