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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Bibliographic Details
Published in:Neurochemistry international 2008-12, Vol.53 (6), p.408-415
Main Authors: Gonzalez, Laura E., Juknat, A. Ana, Venosa, Andrea J., Verrengia, Noemi, Kotler, Mónica L.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Astrocytes
Astrocytes - drug effects
Astrocytes - metabolism
Bax
bcl-2-Associated X Protein - drug effects
bcl-2-Associated X Protein - metabolism
Bcl-X L
bcl-X Protein - drug effects
bcl-X Protein - metabolism
Bcl-X S
Biological and medical sciences
Caspases - drug effects
Caspases - metabolism
Cells, Cultured
Central Nervous System - drug effects
Central Nervous System - metabolism
Central Nervous System - physiopathology
Fundamental and applied biological sciences. Psychology
Manganese
Manganese - toxicity
Manganese Poisoning - metabolism
Manganese Poisoning - physiopathology
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - physiology
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondrial damage
Models, Biological
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases - drug effects
Poly(ADP-ribose) Polymerases - metabolism
Proto-Oncogene Proteins c-bcl-2 - drug effects
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction - drug effects
Signal Transduction - physiology
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2008.09.008