Repositorio UFRO · Omeka S

Ethanol Reduces Amyloid Aggregation In Vitro and Prevents Toxicity in Cell Lines

Primer Autor	Parodi, Jorge
Co-autores	Ormeno, David Romero, Fernando Lopez-Fenner, Julio Avila, Andres Martinez-Torres, Ataulfo
Título	Ethanol Reduces Amyloid Aggregation In Vitro and Prevents Toxicity in Cell Lines
Editorial	ELSEVIER SCIENCE INC
Revista	ARCHIVES OF MEDICAL RESEARCH
Lenguaje	en
Resumen	Background. Alzheimer's disease (AD) alters cognitive functions. A mixture of soluble beta-amyloid aggregates (A beta) are known to act as toxic agents. It has been suggested that moderate alcohol intake reduces the development of neurodegenerative diseases, but the molecular mechanisms leading to this type of prevention have been elusive. We show the ethanol effect in the generation of complex A beta in vitro and the impact on the viability of two cell lines. Methods. The effect of ethanol on the kinetics of beta-amyloid aggregation in vitro was assessed by turbimetry. Soluble- and ethanol-treated beta-amyloid were added to the cell lines HEK and PC-12 to compare their effects on metabolic activity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, we used molecular modeling to assess the impact of exposure to ethanol on the structure of beta-amyloid. Results. Exposure to soluble beta-amyloid was toxic to both cell lines; however, exposing the cells to beta-amyloid aggregated in 10 mmol ethanol prevented the effect. In silico modeling suggested that ethanol alters the dynamics for assembling A beta by disrupting a critical salt bridge between residues Asp 23 and Lys 28, required for amyloid dimerization. Thus, ethanol prevented the formation of complex short (similar to 100 nm) A beta, which are related to higher cell toxicity. Conclusions. Ethanol prevents the formation of stable AD dimers in vitro, thus protecting the cells maintained in culture. Accordingly, in silico modelling predicts that soluble beta-amyloid molecules do not form stable multimers when exposed to ethanol. (C) 2013 IMSS. Published by Elsevier Inc.
Tipo de Recurso	Artículo original
Description	This work was partially supported by FONDEF-CONICYT, Chile, under Grant No. DO5I10416 (FR, JP and DO) and by Direccion de Investigacion UFRO DIUFRO-DI12-0045, D.O. is the recipient of a "Universidad de la Frontera" M.Sc. fellowship. J. L-F. acknowledges the support of Universidad de La Frontera, Vicerrectoria de Investigacion y Postgrado and FONDEF-CONICYT under Grant D06I1081. J.P. was supported by MECESUP UCT0804. AM-T acknowledges support from CONACYT grant 101851. Dr. D.D. Pless kindly edited the manuscript. Este trabajo fue parcialmente apoyado por FONDEF-CONICYT, Chile, bajo la Beca No. DO5I10416 (FR, JP y DO) y por la Dirección de Investigación UFRO DIUFRO-DI12-0045, D.O. es beneficiario de una beca de Maestría de la Universidad de la Frontera. J. L-F. agradece el apoyo de la Universidad de La Frontera, la Vicerrectoría de Investigación y Postgrado y FONDEF-CONICYT bajo la Beca D06I1081. J.P. fue apoyado por MECESUP UCT0804. AM-T agradece el apoyo de la beca CONACYT 101851. El Dr. D.D. Pless amablemente editó el manuscrito.
doi	10.1016/j.arcmed.2012.12.004
Formato Recurso	pdf
Palabras Claves	Alzheimer's disease beta-amyloid Ethanol Molecular simulation ACTIVATED CL-CURRENT ALZHEIMERS-DISEASE BETA-PROTEIN A-BETA SYNAPTIC PLASTICITY ALCOHOL-CONSUMPTION MOLECULAR-DYNAMICS COGNITIVE DECLINE HIPPOCAMPAL MODULATION Enfermedad de Alzheimer beta-amiloide etanol simulación molecular Corriente de cloro activada enfermedad de Alzheimer proteína beta beta alfa plasticidad sináptica consumo de alcohol dinámica molecular deterioro cognitivo hipocampo modulación
Ubicación del archivo	http://dx.doi.org/10.1016/j.arcmed.2012.12.004
Materias	Alzheimer's disease beta-amyloid Ethanol Molecular simulation ACTIVATED CL-CURRENT ALZHEIMERS-DISEASE BETA-PROTEIN A-BETA SYNAPTIC PLASTICITY ALCOHOL-CONSUMPTION MOLECULAR-DYNAMICS COGNITIVE DECLINE HIPPOCAMPAL MODULATION Enfermedad de Alzheimer beta-amiloide etanol simulación molecular Corriente de cloro activada enfermedad de Alzheimer proteína beta beta alfa plasticidad sináptica consumo de alcohol dinámica molecular deterioro cognitivo hipocampo modulación
Disciplinas de la OCDE	Neurociencias Otros Temas de Medicina Básica
Título de la cita (Recomendado-único)	Ethanol Reduces Amyloid Aggregation In Vitro and Prevents Toxicity in Cell Lines
Revista/Libro	ARCHIVES OF MEDICAL RESEARCH
Tipo de ruta	hibrida verde
Access Rights	metadata
Derechos de acceso	metadata
Identificador alternativo	PMID 23291379
Idioma	en
Identificador del recurso (Mandatado-único)	Artículo original
Versión del recurso (Recomendado-único)	versión publicada
Entidad financiadora	ANID CONICYT FONDEF DO5I10416#UFRO DI12-0045#ANID CONICYT FONDEF D06I1081#MECESUP UCT0804#CONACYT 101851
Referencia del Financiador (Mandatado si es aplicable-repetible)	ANID CONICYT FONDEF DO5I10416 UFRO DI12-0045 ANID CONICYT FONDEF D06I1081 MECESUP UCT0804 CONACYT 101851
Editorial	ELSEVIER SCIENCE INC
ISSN	0188-4409
Página de inicio (Recomendado-único)	1
Página final (Recomendado-único)	7
Categoría WOS	Medicina, Investigación y Experimentación Medicine, Research & Experimental
Formato	pdf
Id de Web of Science	WOS:000315070200001