Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family
Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms as...
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paper:paper_01970186_v53_n6-8_p408_Gonzalez2023-06-08T15:20:35Z Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family González, Laura Elisabeth Juknat, Adela Ana Kotler, Mónica Lidia Apoptosis Astrocytes Bax Bcl-XL Bcl-XS Manganese Mitochondrial damage cytochrome c effector caspase manganese nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 protein bcl 2 animal cell animal experiment apoptosis article astrocyte cell death cell membrane depolarization cell structure cell survival controlled study cytoplasm mitochondrion nonhuman priority journal protein degradation protein expression protein secretion rat Animals Animals, Newborn Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Caspases Cells, Cultured Central Nervous System Manganese Manganese Poisoning Membrane Potential, Mitochondrial Mitochondria Models, Biological Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Signal Transduction Rattus Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-1 cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism. © 2008 Elsevier Ltd. All rights reserved. Fil:Gonzalez, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Juknat, A.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. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v53_n6-8_p408_Gonzalez http://hdl.handle.net/20.500.12110/paper_01970186_v53_n6-8_p408_Gonzalez |
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 Astrocytes Bax Bcl-XL Bcl-XS Manganese Mitochondrial damage cytochrome c effector caspase manganese nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 protein bcl 2 animal cell animal experiment apoptosis article astrocyte cell death cell membrane depolarization cell structure cell survival controlled study cytoplasm mitochondrion nonhuman priority journal protein degradation protein expression protein secretion rat Animals Animals, Newborn Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Caspases Cells, Cultured Central Nervous System Manganese Manganese Poisoning Membrane Potential, Mitochondrial Mitochondria Models, Biological Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Signal Transduction Rattus |
spellingShingle |
Apoptosis Astrocytes Bax Bcl-XL Bcl-XS Manganese Mitochondrial damage cytochrome c effector caspase manganese nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 protein bcl 2 animal cell animal experiment apoptosis article astrocyte cell death cell membrane depolarization cell structure cell survival controlled study cytoplasm mitochondrion nonhuman priority journal protein degradation protein expression protein secretion rat Animals Animals, Newborn Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Caspases Cells, Cultured Central Nervous System Manganese Manganese Poisoning Membrane Potential, Mitochondrial Mitochondria Models, Biological Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Signal Transduction Rattus González, Laura Elisabeth Juknat, Adela Ana Kotler, Mónica Lidia Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
topic_facet |
Apoptosis Astrocytes Bax Bcl-XL Bcl-XS Manganese Mitochondrial damage cytochrome c effector caspase manganese nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 protein bcl 2 animal cell animal experiment apoptosis article astrocyte cell death cell membrane depolarization cell structure cell survival controlled study cytoplasm mitochondrion nonhuman priority journal protein degradation protein expression protein secretion rat Animals Animals, Newborn Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Caspases Cells, Cultured Central Nervous System Manganese Manganese Poisoning Membrane Potential, Mitochondrial Mitochondria Models, Biological Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Signal Transduction Rattus |
description |
Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-1 cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism. © 2008 Elsevier Ltd. All rights reserved. |
author |
González, Laura Elisabeth Juknat, Adela Ana Kotler, Mónica Lidia |
author_facet |
González, Laura Elisabeth Juknat, Adela Ana Kotler, Mónica Lidia |
author_sort |
González, Laura Elisabeth |
title |
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
title_short |
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
title_full |
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
title_fullStr |
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
title_full_unstemmed |
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family |
title_sort |
manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the bcl-2 family |
publishDate |
2008 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v53_n6-8_p408_Gonzalez http://hdl.handle.net/20.500.12110/paper_01970186_v53_n6-8_p408_Gonzalez |
work_keys_str_mv |
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_version_ |
1768546580703477760 |