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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-7-3
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pubmed:abstractText |
Neurodegeneration associated with Alzheimer's disease is believed to involve toxicity to beta-amyloid (A beta) and related peptides. Treatment of cultured rat hippocampal neurons with A beta 1-40 (1 microM) or the active fragment A beta 25-35 (1 microM) for 5 days led to a approximately 40-50% decrease in neuronal viability. The hydrophilic antioxidant ascorbic acid (300 microM) and the lipophilic antioxidant 2-mercaptoethanol (10 microM) both protected significantly against A beta neurotoxicity. Despite the protective effects of these antioxidants, both acute and chronic treatments with A beta 25-35 did not increase production of superoxide anions, as monitored with the fluorescent probe hydroethidine. Similarly, overexpression of Cu/Zn-superoxide dismutase using adenovirus-mediated gene transfer did not protect against A beta neurotoxicity. A beta neurotoxicity, however, was prevented in cultures infected with a recombinant, replication-defective adenovirus overexpressing the Ca2+ binding protein calbindin D28k. Transforming growth factor-beta 1 (TGF-beta 1) has been shown to protect neurons against both Ca(2+)- and free radical-mediated neuronal degeneration. We found that A beta neurotoxicity was significantly attenuated by single treatments with TGF-beta 1 (0.1-10 ng/ml) and prevented by repetitive treatments (10 ng/ml/day). The protective effects of TGF-beta 1 were associated with a preservation of mitochondrial potential and function, as determined with rhodamine-123-based microfluorimetry. Because both increased oxidative stress and pathophysiological Ca2+ fluxes can impair mitochondrial function, preservation of mitochondrial potential by TGF-beta 1 could be directly associated with its protection against A beta neurotoxicity. The ability of TGF-beta 1 to increase the expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL is discussed in this context.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6-Cyano-7-nitroquinoxaline-2,3-dione,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Protein, Vitamin...,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Mercaptoethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-40),
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (25-35),
http://linkedlifedata.com/resource/pubmed/chemical/calbindin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0026-895X
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pubmed:author |
pubmed-author:BindokasV PVP,
pubmed-author:BoiseL HLH,
pubmed-author:GalindoM FMF,
pubmed-author:GhadgeG DGD,
pubmed-author:JordánJJ,
pubmed-author:KrajewskiSS,
pubmed-author:MillerR JRJ,
pubmed-author:PrehnJ HJH,
pubmed-author:ReedJ CJC,
pubmed-author:RoosR PRP,
pubmed-author:ThompsonC BCB
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pubmed:issnType |
Print
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
319-28
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8632765-6-Cyano-7-nitroquinoxaline-2,3-dione,
pubmed-meshheading:8632765-Adenoviridae,
pubmed-meshheading:8632765-Amyloid beta-Peptides,
pubmed-meshheading:8632765-Animals,
pubmed-meshheading:8632765-Antioxidants,
pubmed-meshheading:8632765-Ascorbic Acid,
pubmed-meshheading:8632765-Calcium-Binding Protein, Vitamin D-Dependent,
pubmed-meshheading:8632765-Cell Survival,
pubmed-meshheading:8632765-Cells, Cultured,
pubmed-meshheading:8632765-Dizocilpine Maleate,
pubmed-meshheading:8632765-Dose-Response Relationship, Drug,
pubmed-meshheading:8632765-Embryo, Mammalian,
pubmed-meshheading:8632765-Genetic Vectors,
pubmed-meshheading:8632765-Hippocampus,
pubmed-meshheading:8632765-Mercaptoethanol,
pubmed-meshheading:8632765-Neurons,
pubmed-meshheading:8632765-Neurotoxins,
pubmed-meshheading:8632765-Peptide Fragments,
pubmed-meshheading:8632765-Rats,
pubmed-meshheading:8632765-Recombinant Proteins,
pubmed-meshheading:8632765-Superoxide Dismutase,
pubmed-meshheading:8632765-Synaptic Transmission,
pubmed-meshheading:8632765-Tetrodotoxin,
pubmed-meshheading:8632765-Transfection,
pubmed-meshheading:8632765-Transforming Growth Factor beta
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pubmed:year |
1996
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pubmed:articleTitle |
Protective effect of transforming growth factor-beta 1 on beta-amyloid neurotoxicity in rat hippocampal neurons.
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pubmed:affiliation |
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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