The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells

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 deg...

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Autor principal: Alaimo, A.
Otros Autores: Gorojod, R.M, Kotler, M.L
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2011
Acceso en línea:Registro en Scopus
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024 7 |2 cas  |a 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 
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100 1 |a Alaimo, A. 
245 1 4 |a The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells 
260 |c 2011 
270 1 0 |m Kotler, M.L.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Avda. Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina; email: kotler@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas, 5406, PIP Nos. 02631 
536 |a Detalles de la financiación: This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET (PIP Nos. 02631 and 5406). The authors thank Dr. Elizabeth Jares-Erijman and Francisco Guaimas from the Organic Chemistry Department, FCEN-UBA, for their excellent assistance in obtaining fluorescence microscopy images. The authors are very grateful to Dr. Elba Vazquez for the critical reading of the manuscript. We acknowledge the contribution of Dr. Mónica Costas for providing Bid primary antibody and Dr. Pablo Mele from the Human Medicine Department, Faculty of Medicine, UBA for providing the OxPhos (Complex III) primary antibody. A.A and R.M.G. thanks CONICET for a studentship. M.L.K. is research member of CONICET. Appendix A 
593 |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Avda. Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina 
690 1 0 |a APOPTOSIS 
690 1 0 |a C6 CELLS 
690 1 0 |a CASPASES 
690 1 0 |a MANGANESE 
690 1 0 |a MITOCHONDRIA 
690 1 0 |a CASPASE 3 
690 1 0 |a CASPASE 7 
690 1 0 |a CASPASE 8 
690 1 0 |a CASPASE 9 
690 1 0 |a CYTOCHROME C 
690 1 0 |a FAS LIGAND 
690 1 0 |a MANGANESE 
690 1 0 |a MITOCHONDRIAL PERMEABILITY TRANSITION PORE 
690 1 0 |a NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 
690 1 0 |a PROTEIN BCL 2 
690 1 0 |a PROTEIN BID 
690 1 0 |a REACTIVE OXYGEN METABOLITE 
690 1 0 |a ANIMAL CELL 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a ASTROCYTOMA CELL 
690 1 0 |a CELL DEATH 
690 1 0 |a CELL VIABILITY 
690 1 0 |a CHROMATIN CONDENSATION 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a ENZYME ACTIVATION 
690 1 0 |a MITOCHONDRIAL MEMBRANE POTENTIAL 
690 1 0 |a MITOCHONDRION 
690 1 0 |a NEUROTOXICITY 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN CLEAVAGE 
690 1 0 |a PROTEIN SECRETION 
690 1 0 |a RAT 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a ANIMALS 
690 1 0 |a APOPTOSIS 
690 1 0 |a ASTROCYTOMA 
690 1 0 |a BLOTTING, WESTERN 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a MANGANESE 
690 1 0 |a MICROSCOPY, FLUORESCENCE 
690 1 0 |a RATS 
690 1 0 |a SUBCELLULAR FRACTIONS 
690 1 0 |a RATTUS 
700 1 |a Gorojod, R.M. 
700 1 |a Kotler, M.L. 
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