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The action of ethanol on G protein. <i>In silico</i> and cellular/molecular evidences

¹ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
² Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
³ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
⁴ Universidad Nacional Autonoma de Mexico, Centro de Nanociencias y Nanotecnologia, Ensenada, Mexico
⁵ Laboratorio de Virus Oncológicos en Reproducción, BIOREN-CEGIN, Universidad de La Frontera, Temuco, Chile
⁶ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
⁷ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
⁸ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
⁹ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile
¹⁰ Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepción, Concepcion, Chile
¹¹ Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello Sede Concepcion, Talcahuano, Chile

Advances in Bioscience and Biotechnology·Volume 04 (2013)·Pages 665–673·Published 27 May 2013·DOI10.4236/abb.2013.45087

Abstract

Ethanol (EtOH) enhances glycinergic currents in the central nervous system (CNS). Because evidence for an interaction between the α 1 subunit of the glycine receptor ( α 1GlyR) and the G protein G βγ subunit exists in vitro and because cAMP levels are known to increase in response to EtOH, we wanted to investigate the interaction between G βγ and α 1GlyR in response to EtOH treatment in HEK293 cells and to explore the possible sites of interaction between EtOH and the G α s subunit. His pull-down assays in GlyR-His6-transfected HEK293 cells incubated with ethanol or propofol revealed that only EtOH treatment increased the binding of G βγ heterodimers to α 1GlyR. Using molecular modelling (protein structure prediction), was modelled the hG α s protein for the first time and validated this model by site-directed mutagenesis. By molecular docking, we identified some potential regions of interaction between hG α s and EtOH that are located on the SIII and SI regions of the G α s. Therefore, we conclude that ethanol increases the interaction between α 1GlyR and G βγ in HEK293 cells, an effect that might be attributed to the interaction between EtOH and hG α s, which consequently stimulates hG α s.

KeywordsAlcoholismEthanolGlycine ReceptorG ProteinsSignals Transduction

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The action of ethanol on G protein. <i>In silico</i> and cellular/molecular evidences

Abstract

References (28)