Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells

Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our gr...

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Autores principales:	Alaimo, Agustina, Porte Alcon, Soledad, Kotler, Mónica Lidia
Publicado:	2017
Materias:	Apoptosis Cathepsins Glia Lysosomes Manganese Parkinsonism bafilomycin A1 caspase 3 caspase 7 caspase 8 caspase 9 cathepsin cathepsin B cathepsin D cytochrome c death receptor Fas ligand manganese pepstatin protein Bid Bid protein, rat macrolide Tnfsf6 protein, rat animal cell animal experiment animal model animal tissue apoptosis Article controlled study corpus striatum cytosol enzyme activation enzyme release glia cell immunocytochemistry immunohistochemistry in vivo study lysosome lysosome membrane male membrane permeability mitochondrion molecular biology nonhuman oxidative stress priority journal protein cleavage protein expression protein transport rat substantia nigra pars compacta upregulation Western blotting animal drug effect glia metabolism pathology physiology signal transduction Sprague Dawley rat tumor cell line Animals BH3 Interacting Domain Death Agonist Protein Caspase 3 Caspase 7 Cathepsin D Cell Line, Tumor Cytosol Fas Ligand Protein Macrolides Male Mitochondria Neuroglia Protein Transport Rats, Sprague-Dawley Signal Transduction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v91_n9_p3065_Gorojod http://hdl.handle.net/20.500.12110/paper_03405761_v91_n9_p3065_Gorojod
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_03405761_v91_n9_p3065_Gorojod2023-06-08T15:34:06Z Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells Alaimo, Agustina Porte Alcon, Soledad Kotler, Mónica Lidia Apoptosis Cathepsins Glia Lysosomes Manganese Parkinsonism bafilomycin A1 caspase 3 caspase 7 caspase 8 caspase 9 cathepsin cathepsin B cathepsin D cytochrome c death receptor Fas ligand manganese pepstatin protein Bid Bid protein, rat caspase 3 caspase 7 cathepsin D Fas ligand macrolide manganese protein Bid Tnfsf6 protein, rat animal cell animal experiment animal model animal tissue apoptosis Article controlled study corpus striatum cytosol enzyme activation enzyme release glia cell immunocytochemistry immunohistochemistry in vivo study lysosome lysosome membrane male membrane permeability mitochondrion molecular biology nonhuman oxidative stress priority journal protein cleavage protein expression protein transport rat substantia nigra pars compacta upregulation Western blotting animal apoptosis drug effect glia lysosome metabolism mitochondrion pathology physiology signal transduction Sprague Dawley rat tumor cell line Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Caspase 3 Caspase 7 Cathepsin D Cell Line, Tumor Cytosol Fas Ligand Protein Lysosomes Macrolides Male Manganese Mitochondria Neuroglia Protein Transport Rats, Sprague-Dawley Signal Transduction Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our group have proved that Mn induces oxidative stress-mediated apoptosis in astrocytoma C6 cells. In the present study we described how cathepsins impact on different steps of each apoptotic cascade. Evidence obtained demonstrated that Mn generates lysosomal membrane permeabilization (LMP) and cathepsin release. Both cathepsins B (Ca-074 Me) and D (Pepstatin A) inhibitors as well as Bafilomycin A1 prevented caspases-3, -7, -8 and -9 activation, FasL upregulation, Bid cleavage, Δφm disruption and cytochrome c release. Results from in vivo studies showed that intrastriatal Mn injection increased cathepsin D levels from corpus striatum and substantia nigra pars compacta. Our results point to LMP and lysosomal cathepsins as key mediators in the apoptotic process triggered by Mn. These findings highlight the relevance of targeting the lysosomal pathway for Manganism therapy. © 2017, Springer-Verlag Berlin Heidelberg. Fil:Alaimo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Porte Alcon, S. 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. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v91_n9_p3065_Gorojod http://hdl.handle.net/20.500.12110/paper_03405761_v91_n9_p3065_Gorojod
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 Cathepsins Glia Lysosomes Manganese Parkinsonism bafilomycin A1 caspase 3 caspase 7 caspase 8 caspase 9 cathepsin cathepsin B cathepsin D cytochrome c death receptor Fas ligand manganese pepstatin protein Bid Bid protein, rat caspase 3 caspase 7 cathepsin D Fas ligand macrolide manganese protein Bid Tnfsf6 protein, rat animal cell animal experiment animal model animal tissue apoptosis Article controlled study corpus striatum cytosol enzyme activation enzyme release glia cell immunocytochemistry immunohistochemistry in vivo study lysosome lysosome membrane male membrane permeability mitochondrion molecular biology nonhuman oxidative stress priority journal protein cleavage protein expression protein transport rat substantia nigra pars compacta upregulation Western blotting animal apoptosis drug effect glia lysosome metabolism mitochondrion pathology physiology signal transduction Sprague Dawley rat tumor cell line Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Caspase 3 Caspase 7 Cathepsin D Cell Line, Tumor Cytosol Fas Ligand Protein Lysosomes Macrolides Male Manganese Mitochondria Neuroglia Protein Transport Rats, Sprague-Dawley Signal Transduction
spellingShingle	Apoptosis Cathepsins Glia Lysosomes Manganese Parkinsonism bafilomycin A1 caspase 3 caspase 7 caspase 8 caspase 9 cathepsin cathepsin B cathepsin D cytochrome c death receptor Fas ligand manganese pepstatin protein Bid Bid protein, rat caspase 3 caspase 7 cathepsin D Fas ligand macrolide manganese protein Bid Tnfsf6 protein, rat animal cell animal experiment animal model animal tissue apoptosis Article controlled study corpus striatum cytosol enzyme activation enzyme release glia cell immunocytochemistry immunohistochemistry in vivo study lysosome lysosome membrane male membrane permeability mitochondrion molecular biology nonhuman oxidative stress priority journal protein cleavage protein expression protein transport rat substantia nigra pars compacta upregulation Western blotting animal apoptosis drug effect glia lysosome metabolism mitochondrion pathology physiology signal transduction Sprague Dawley rat tumor cell line Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Caspase 3 Caspase 7 Cathepsin D Cell Line, Tumor Cytosol Fas Ligand Protein Lysosomes Macrolides Male Manganese Mitochondria Neuroglia Protein Transport Rats, Sprague-Dawley Signal Transduction Alaimo, Agustina Porte Alcon, Soledad Kotler, Mónica Lidia Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
topic_facet	Apoptosis Cathepsins Glia Lysosomes Manganese Parkinsonism bafilomycin A1 caspase 3 caspase 7 caspase 8 caspase 9 cathepsin cathepsin B cathepsin D cytochrome c death receptor Fas ligand manganese pepstatin protein Bid Bid protein, rat caspase 3 caspase 7 cathepsin D Fas ligand macrolide manganese protein Bid Tnfsf6 protein, rat animal cell animal experiment animal model animal tissue apoptosis Article controlled study corpus striatum cytosol enzyme activation enzyme release glia cell immunocytochemistry immunohistochemistry in vivo study lysosome lysosome membrane male membrane permeability mitochondrion molecular biology nonhuman oxidative stress priority journal protein cleavage protein expression protein transport rat substantia nigra pars compacta upregulation Western blotting animal apoptosis drug effect glia lysosome metabolism mitochondrion pathology physiology signal transduction Sprague Dawley rat tumor cell line Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Caspase 3 Caspase 7 Cathepsin D Cell Line, Tumor Cytosol Fas Ligand Protein Lysosomes Macrolides Male Manganese Mitochondria Neuroglia Protein Transport Rats, Sprague-Dawley Signal Transduction
description	Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our group have proved that Mn induces oxidative stress-mediated apoptosis in astrocytoma C6 cells. In the present study we described how cathepsins impact on different steps of each apoptotic cascade. Evidence obtained demonstrated that Mn generates lysosomal membrane permeabilization (LMP) and cathepsin release. Both cathepsins B (Ca-074 Me) and D (Pepstatin A) inhibitors as well as Bafilomycin A1 prevented caspases-3, -7, -8 and -9 activation, FasL upregulation, Bid cleavage, Δφm disruption and cytochrome c release. Results from in vivo studies showed that intrastriatal Mn injection increased cathepsin D levels from corpus striatum and substantia nigra pars compacta. Our results point to LMP and lysosomal cathepsins as key mediators in the apoptotic process triggered by Mn. These findings highlight the relevance of targeting the lysosomal pathway for Manganism therapy. © 2017, Springer-Verlag Berlin Heidelberg.
author	Alaimo, Agustina Porte Alcon, Soledad Kotler, Mónica Lidia
author_facet	Alaimo, Agustina Porte Alcon, Soledad Kotler, Mónica Lidia
author_sort	Alaimo, Agustina
title	Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
title_short	Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
title_full	Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
title_fullStr	Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
title_full_unstemmed	Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
title_sort	interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v91_n9_p3065_Gorojod http://hdl.handle.net/20.500.12110/paper_03405761_v91_n9_p3065_Gorojod
work_keys_str_mv	AT alaimoagustina interplaybetweenlysosomalmitochondrialanddeathreceptorpathwaysduringmanganeseinducedapoptosisinglialcells AT portealconsoledad interplaybetweenlysosomalmitochondrialanddeathreceptorpathwaysduringmanganeseinducedapoptosisinglialcells AT kotlermonicalidia interplaybetweenlysosomalmitochondrialanddeathreceptorpathwaysduringmanganeseinducedapoptosisinglialcells
_version_	1768544687154528256

Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells

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