Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder

NEUROBIOLOGY OF DISEASE

卷:44

Article

Bychkov, E. R.¹  Ahmed, M. R.¹  Gurevich, V. V.¹  Benovic, J. L.²  Gurevich, E. V.¹ 

[1] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA

[2] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA

关键词: G protein-coupled receptor kinase;    Arrestin;    Schizophrenia;    Schizoaffective disorder;    Postmortem;    Protein expression;    RNAse protection assay;    mRNA expression;   

DOI  :  10.1016/j.nbd.2011.07.009

来源: Elsevier

【 摘 要 】

Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

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