Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells
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 ev...
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todo:paper_03043940_v554_n_p76_Alaimo2023-10-03T15:20:21Z Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells Alaimo, A. Gorojod, R.M. Miglietta, E.A. Villarreal, A. Ramos, A.J. Kotler, M.L. Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics caspase 3 caspase 7 caspase 9 drp 1 protein glial fibrillary acidic protein manganese mitofusin 2 opa 1 protein protein Bax protein bcl 2 protein S100B unclassified drug apoptosis article astrocyte cell structure cell viability chromatin condensation controlled study enzyme activation glioma human human cell immunocytochemistry in vitro study mitochondrial dynamics mitochondrial membrane potential neurotoxicity priority journal Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics Apoptosis Astrocytes Cell Line, Tumor Environmental Pollutants Humans Manganese Membrane Potential, Mitochondrial Mitochondrial Dynamics 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. © 2013 Elsevier Ireland Ltd. Fil:Alaimo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Villarreal, 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03043940_v554_n_p76_Alaimo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics caspase 3 caspase 7 caspase 9 drp 1 protein glial fibrillary acidic protein manganese mitofusin 2 opa 1 protein protein Bax protein bcl 2 protein S100B unclassified drug apoptosis article astrocyte cell structure cell viability chromatin condensation controlled study enzyme activation glioma human human cell immunocytochemistry in vitro study mitochondrial dynamics mitochondrial membrane potential neurotoxicity priority journal Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics Apoptosis Astrocytes Cell Line, Tumor Environmental Pollutants Humans Manganese Membrane Potential, Mitochondrial Mitochondrial Dynamics |
| spellingShingle |
Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics caspase 3 caspase 7 caspase 9 drp 1 protein glial fibrillary acidic protein manganese mitofusin 2 opa 1 protein protein Bax protein bcl 2 protein S100B unclassified drug apoptosis article astrocyte cell structure cell viability chromatin condensation controlled study enzyme activation glioma human human cell immunocytochemistry in vitro study mitochondrial dynamics mitochondrial membrane potential neurotoxicity priority journal Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics Apoptosis Astrocytes Cell Line, Tumor Environmental Pollutants Humans Manganese Membrane Potential, Mitochondrial Mitochondrial Dynamics Alaimo, A. Gorojod, R.M. Miglietta, E.A. Villarreal, A. Ramos, A.J. Kotler, M.L. Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| topic_facet |
Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics caspase 3 caspase 7 caspase 9 drp 1 protein glial fibrillary acidic protein manganese mitofusin 2 opa 1 protein protein Bax protein bcl 2 protein S100B unclassified drug apoptosis article astrocyte cell structure cell viability chromatin condensation controlled study enzyme activation glioma human human cell immunocytochemistry in vitro study mitochondrial dynamics mitochondrial membrane potential neurotoxicity priority journal Apoptosis Astrocytes Human Gli36 cell line Manganese toxicity Manganism Mitochondrial dynamics Apoptosis Astrocytes Cell Line, Tumor Environmental Pollutants Humans Manganese Membrane Potential, Mitochondrial Mitochondrial Dynamics |
| description |
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. © 2013 Elsevier Ireland Ltd. |
| format |
JOUR |
| author |
Alaimo, A. Gorojod, R.M. Miglietta, E.A. Villarreal, A. Ramos, A.J. Kotler, M.L. |
| author_facet |
Alaimo, A. Gorojod, R.M. Miglietta, E.A. Villarreal, A. Ramos, A.J. Kotler, M.L. |
| author_sort |
Alaimo, A. |
| title |
Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| title_short |
Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| title_full |
Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| title_fullStr |
Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| title_full_unstemmed |
Manganese induces mitochondrial dynamics impairment and apoptotic cell death: A study in human Gli36 cells |
| title_sort |
manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human gli36 cells |
| url |
http://hdl.handle.net/20.500.12110/paper_03043940_v554_n_p76_Alaimo |
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