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Artículo

Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human Gli36 cells

Alaimo, AgustinaIcon ; Gorojod, Roxana MayraIcon ; Miglietta, Esteban AlbertoIcon ; Villarreal, AlejandroIcon ; Ramos, Alberto JavierIcon ; Kotler, Monica LidiaIcon
Fecha de publicación: 10/2013
Editorial: Elsevier Ireland
Revista: Neuroscience Letters
ISSN: 0304-3940
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

Manganese (Mn) is an essential trace element due to its participation in many physiological processes. However, overexposure to this metal leads to a neurological disorder known as Manganism whose clinical manifestations and molecular mechanisms resemble Parkinson's disease. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity being the mitochondria the most affected organelles. The aim of this study was to investigate the possible mitochondrial dynamics alterations in Mn-exposed human astrocytes. Therefore, we employed Gli36 cells which express the astrocytic markers GFAP and S100B. We demonstrated that Mn triggers the mitochondrial apoptotic pathway revealed by increased Bax/Bcl-2 ratio, by the loss of mitochondrial membrane potential and by caspase-9 activation. This apoptotic program may be in turn responsible of caspase-3/7 activation, PARP-1 cleavage, chromatin condensation and fragmentation. In addition, we determined that Mn induces deregulation in mitochondria-shaping proteins (Opa-1, Mfn-2 and Drp-1) expression levels in parallel with the disruption of the mitochondrial network toward to an exacerbated fragmentation. Since mitochondrial dynamics is altered in several neurodegenerative diseases, these proteins could become future targets to be considered in Manganism treatment.
Palabras clave: Apoptosis , Astrocytes
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/12159
URL: http://www.sciencedirect.com/science/article/pii/S0304394013007945
DOI: http://dx.doi.org/10.1016/j.neulet.2013.08.061
Colecciones
Articulos(IBCN)
Articulos de INST.DE BIOLO.CEL.Y NEURCS."PROF.E.DE ROBERTIS"
Citación
Alaimo, Agustina; Gorojod, Roxana Mayra; Miglietta, Esteban Alberto; Villarreal, Alejandro; Ramos, Alberto Javier; et al.; Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human Gli36 cells; Elsevier Ireland; Neuroscience Letters; 554; 10-2013; 76-81
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