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Abstract:

Manganese (Mn) is a trace element known to be essential for maintaining the proper function and regulation of many biochemical and cellular reactions. However, chronic exposure to high levels of Mn in occupational or environmental settings can lead to its accumulation in the brain resulting in a degenerative brain disorder referred to as Manganism. Astrocytes are the main Mn store in the central nervous system and several lines of evidence implicate these cells as major players in the role of Manganism development. In the present study, we employed rat astrocytoma C6 cells as a sensitive experimental model for investigating molecular mechanisms involved in Mn neurotoxicity. Our results show that C6 cells undergo reactive oxygen species-mediated apoptotic cell death involving caspase-8 and mitochondrial-mediated pathways in response to Mn. Exposed cells exhibit typical apoptotic features, such as chromatin condensation, cell shrinkage, membrane blebbing, caspase-3 activation and caspase-specific cleavage of the endogenous substrate poly (ADP-ribose) polymerase. Participation of the caspase-8 dependent pathway was assessed by increased levels of FasL, caspase-8 activation and Bid cleavage. The involvement of the mitochondrial pathway was demonstrated by the disruption of the mitochondrial membrane potential, the opening of the mitochondrial permeability transition pore, cytochrome c release, caspase-9 activation and the increased mitochondrial levels of the pro-apoptotic Bcl-2 family proteins. In addition, our data also shows for the first time that mitochondrial fragmentation plays a relevant role in Mn-induced apoptosis. Taking together, these findings contribute to a deeper elucidation of the molecular signaling mechanisms underlying Mn-induced apoptosis. © 2011 Elsevier B.V. All rights reserved.

Registro:

Documento: Artículo
Título:The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells
Autor:Alaimo, A.; Gorojod, R.M.; Kotler, M.L.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Avda. Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina
Palabras clave:Apoptosis; C6 cells; Caspases; Manganese; Mitochondria; caspase 3; caspase 7; caspase 8; caspase 9; cytochrome c; Fas ligand; manganese; mitochondrial permeability transition pore; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein bcl 2; protein Bid; reactive oxygen metabolite; animal cell; apoptosis; article; astrocytoma cell; cell death; cell viability; chromatin condensation; controlled study; enzyme activation; mitochondrial membrane potential; mitochondrion; neurotoxicity; nonhuman; priority journal; protein cleavage; protein secretion; rat; signal transduction; Animals; Apoptosis; Astrocytoma; Blotting, Western; Cell Line, Tumor; Manganese; Microscopy, Fluorescence; Rats; Subcellular Fractions; Rattus
Año:2011
Volumen:59
Número:2
Página de inicio:297
Página de fin:308
DOI: http://dx.doi.org/10.1016/j.neuint.2011.06.001
Título revista:Neurochemistry International
Título revista abreviado:Neurochem. Int.
ISSN:01970186
CODEN:NEUID
CAS:caspase 3, 169592-56-7; caspase 7, 189258-14-8; caspase 9, 180189-96-2; cytochrome c, 9007-43-6, 9064-84-0; manganese, 16397-91-4, 7439-96-5; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; protein Bid, 260235-79-8; protein bcl 2, 219306-68-0; Manganese, 7439-96-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v59_n2_p297_Alaimo

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Citas:

---------- APA ----------
Alaimo, A., Gorojod, R.M. & Kotler, M.L. (2011) . The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells. Neurochemistry International, 59(2), 297-308.
http://dx.doi.org/10.1016/j.neuint.2011.06.001
---------- CHICAGO ----------
Alaimo, A., Gorojod, R.M., Kotler, M.L. "The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells" . Neurochemistry International 59, no. 2 (2011) : 297-308.
http://dx.doi.org/10.1016/j.neuint.2011.06.001
---------- MLA ----------
Alaimo, A., Gorojod, R.M., Kotler, M.L. "The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells" . Neurochemistry International, vol. 59, no. 2, 2011, pp. 297-308.
http://dx.doi.org/10.1016/j.neuint.2011.06.001
---------- VANCOUVER ----------
Alaimo, A., Gorojod, R.M., Kotler, M.L. The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells. Neurochem. Int. 2011;59(2):297-308.
http://dx.doi.org/10.1016/j.neuint.2011.06.001