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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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v59_n2_p297_Alaimo http://hdl.handle.net/20.500.12110/paper_01970186_v59_n2_p297_Alaimo |
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paper:paper_01970186_v59_n2_p297_Alaimo2025-07-30T17:59:02Z The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells Alaimo, Agustina Kotler, Mónica Lidia 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 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. Fil:Alaimo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kotler, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v59_n2_p297_Alaimo http://hdl.handle.net/20.500.12110/paper_01970186_v59_n2_p297_Alaimo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Alaimo, Agustina Kotler, Mónica Lidia The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| topic_facet |
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 |
| description |
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. |
| author |
Alaimo, Agustina Kotler, Mónica Lidia |
| author_facet |
Alaimo, Agustina Kotler, Mónica Lidia |
| author_sort |
Alaimo, Agustina |
| title |
The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| title_short |
The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| title_full |
The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| title_fullStr |
The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| title_full_unstemmed |
The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells |
| title_sort |
extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma c6 cells |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v59_n2_p297_Alaimo http://hdl.handle.net/20.500.12110/paper_01970186_v59_n2_p297_Alaimo |
| work_keys_str_mv |
AT alaimoagustina theextrinsicandintrinsicapoptoticpathwaysareinvolvedinmanganesetoxicityinratastrocytomac6cells AT kotlermonicalidia theextrinsicandintrinsicapoptoticpathwaysareinvolvedinmanganesetoxicityinratastrocytomac6cells AT alaimoagustina extrinsicandintrinsicapoptoticpathwaysareinvolvedinmanganesetoxicityinratastrocytomac6cells AT kotlermonicalidia extrinsicandintrinsicapoptoticpathwaysareinvolvedinmanganesetoxicityinratastrocytomac6cells |
| _version_ |
1840322891064803328 |