Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes
During oxidative stress, cell apoptosis is promoted through the mitochondrial death pathway. Increased reactive oxygen species (ROS) are linked to excess cell loss and mediate the induction of apoptosis in various cell types. However, the role of ROS in the apoptotic pathway has not been clearly est...
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todo:paper_07423098_v38_n2_p84_Juknat2023-10-03T15:38:24Z Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes Juknat, A.A. Del Valle Armanino Méndez, M. Quaglino, A. Fameli, C.I. Mena, M. Kotler, M.L. Antioxidant enzymes Antioxidants Apoptosis Astrocyte Bax Caspase-3 Hydrogen peroxide Melatonin Reactive oxygen species acetylcysteine caspase 3 dichlorofluorescein DNA fragment glutathione hydrogen peroxide melatonin protein Bax reactive oxygen metabolite animal cell antioxidant activity apoptosis article astrocyte cell culture cell loss cell protection cell size cell structure cell type cell viability concentration response controlled study enzyme activation gene expression regulation hormone action mitochondrion nonhuman oxidative stress rat Animals Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Blotting, Western Caspase 3 Caspases Dose-Response Relationship, Drug Gene Expression Regulation Hydrogen Peroxide Melatonin Oxidants Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Time Factors During oxidative stress, cell apoptosis is promoted through the mitochondrial death pathway. Increased reactive oxygen species (ROS) are linked to excess cell loss and mediate the induction of apoptosis in various cell types. However, the role of ROS in the apoptotic pathway has not been clearly established. The aims of this study were to investigate the biochemical and morphological responses of rat astrocytes to hydrogen peroxide-mediated cell death and to define the role that melatonin might play in the apoptotic cascade. Hydrogen peroxide (H 2O 2; 0.1-1.0 mM) significantly reduced cell viability. Astrocyte death was associated with enhanced ROS production in a dose-dependent manner, as measured by 2′,7′- dichlorofluorescein fluorescence. H 2O 2-induced cell death was found to be mediated through an apoptotic pathway as treated cells exhibited cell shrinkage, nuclear condensation and marked DNA fragmentation. H 2O 2 also triggered caspase-3 activation and Bax expression. The ability of different antioxidants to prevent H 2O 2-induced apoptosis was examined by pre-incubating rat astrocytes with N-acetylcysteine (10 mM), glutathione (0.5 mM) or melatonin (0.1 mM and 10 nM). Results showed that N-acetylcysteine and glutathion can protect astrocytes against ROS accumulation and caspase-3 activation, whereas 0.1 mM melatonin can inhibit H 2O 2-induced apoptosis by regulating Bax expression and by inhibiting caspase-3 activation. Antiapoptotic effect of 10 nM melatonin associated to inhibition of Bax expression, give rise to new therapeutic approaches. Copyright © Blackwell Munksgaard, 2004. Fil:Juknat, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del Valle Armanino Méndez, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Quaglino, 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_07423098_v38_n2_p84_Juknat |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antioxidant enzymes Antioxidants Apoptosis Astrocyte Bax Caspase-3 Hydrogen peroxide Melatonin Reactive oxygen species acetylcysteine caspase 3 dichlorofluorescein DNA fragment glutathione hydrogen peroxide melatonin protein Bax reactive oxygen metabolite animal cell antioxidant activity apoptosis article astrocyte cell culture cell loss cell protection cell size cell structure cell type cell viability concentration response controlled study enzyme activation gene expression regulation hormone action mitochondrion nonhuman oxidative stress rat Animals Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Blotting, Western Caspase 3 Caspases Dose-Response Relationship, Drug Gene Expression Regulation Hydrogen Peroxide Melatonin Oxidants Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Time Factors |
| spellingShingle |
Antioxidant enzymes Antioxidants Apoptosis Astrocyte Bax Caspase-3 Hydrogen peroxide Melatonin Reactive oxygen species acetylcysteine caspase 3 dichlorofluorescein DNA fragment glutathione hydrogen peroxide melatonin protein Bax reactive oxygen metabolite animal cell antioxidant activity apoptosis article astrocyte cell culture cell loss cell protection cell size cell structure cell type cell viability concentration response controlled study enzyme activation gene expression regulation hormone action mitochondrion nonhuman oxidative stress rat Animals Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Blotting, Western Caspase 3 Caspases Dose-Response Relationship, Drug Gene Expression Regulation Hydrogen Peroxide Melatonin Oxidants Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Time Factors Juknat, A.A. Del Valle Armanino Méndez, M. Quaglino, A. Fameli, C.I. Mena, M. Kotler, M.L. Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| topic_facet |
Antioxidant enzymes Antioxidants Apoptosis Astrocyte Bax Caspase-3 Hydrogen peroxide Melatonin Reactive oxygen species acetylcysteine caspase 3 dichlorofluorescein DNA fragment glutathione hydrogen peroxide melatonin protein Bax reactive oxygen metabolite animal cell antioxidant activity apoptosis article astrocyte cell culture cell loss cell protection cell size cell structure cell type cell viability concentration response controlled study enzyme activation gene expression regulation hormone action mitochondrion nonhuman oxidative stress rat Animals Apoptosis Astrocytes bcl-2-Associated X Protein bcl-X Protein Blotting, Western Caspase 3 Caspases Dose-Response Relationship, Drug Gene Expression Regulation Hydrogen Peroxide Melatonin Oxidants Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Time Factors |
| description |
During oxidative stress, cell apoptosis is promoted through the mitochondrial death pathway. Increased reactive oxygen species (ROS) are linked to excess cell loss and mediate the induction of apoptosis in various cell types. However, the role of ROS in the apoptotic pathway has not been clearly established. The aims of this study were to investigate the biochemical and morphological responses of rat astrocytes to hydrogen peroxide-mediated cell death and to define the role that melatonin might play in the apoptotic cascade. Hydrogen peroxide (H 2O 2; 0.1-1.0 mM) significantly reduced cell viability. Astrocyte death was associated with enhanced ROS production in a dose-dependent manner, as measured by 2′,7′- dichlorofluorescein fluorescence. H 2O 2-induced cell death was found to be mediated through an apoptotic pathway as treated cells exhibited cell shrinkage, nuclear condensation and marked DNA fragmentation. H 2O 2 also triggered caspase-3 activation and Bax expression. The ability of different antioxidants to prevent H 2O 2-induced apoptosis was examined by pre-incubating rat astrocytes with N-acetylcysteine (10 mM), glutathione (0.5 mM) or melatonin (0.1 mM and 10 nM). Results showed that N-acetylcysteine and glutathion can protect astrocytes against ROS accumulation and caspase-3 activation, whereas 0.1 mM melatonin can inhibit H 2O 2-induced apoptosis by regulating Bax expression and by inhibiting caspase-3 activation. Antiapoptotic effect of 10 nM melatonin associated to inhibition of Bax expression, give rise to new therapeutic approaches. Copyright © Blackwell Munksgaard, 2004. |
| format |
JOUR |
| author |
Juknat, A.A. Del Valle Armanino Méndez, M. Quaglino, A. Fameli, C.I. Mena, M. Kotler, M.L. |
| author_facet |
Juknat, A.A. Del Valle Armanino Méndez, M. Quaglino, A. Fameli, C.I. Mena, M. Kotler, M.L. |
| author_sort |
Juknat, A.A. |
| title |
Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| title_short |
Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| title_full |
Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| title_fullStr |
Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| title_full_unstemmed |
Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes |
| title_sort |
melatonin prevents hydrogen peroxide-induced bax expression in cultured rat astrocytes |
| url |
http://hdl.handle.net/20.500.12110/paper_07423098_v38_n2_p84_Juknat |
| work_keys_str_mv |
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