Abstract
Expression of the growth arrest DNA damage-inducible protein, GADD45, has recently been reported to be induced by a wide range of stimuli, especially those that produce a high level of base pair damage. We have investigated the expression of GADD45 in brain tissue obtained from patients suffering from Alzheimer's disease (AD). Our results demonstrate that many neurons express the GADD45 protein, and that expression of this protein in neurons is associated with expression of the anti-apoptotic protein Bcl-2, and the presence of DNA damage, but not closely associated with tangle-bearing neurons. Additionally, cell lines overexpressing this protein confer resistance to apoptosis induced by DNA damage agent, suggesting that this protein may participate in cell survival mechanisms.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / metabolism*
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Apoptosis / drug effects
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Apoptosis / physiology*
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Brain / metabolism
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Brain / pathology
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Camptothecin / pharmacology
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Cell Death / drug effects
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Cell Death / genetics
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Cell Line
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DNA Fragmentation
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Enzyme Inhibitors / pharmacology
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GADD45 Proteins
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Gene Expression
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Humans
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Immunohistochemistry
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Intracellular Signaling Peptides and Proteins
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Neurofibrillary Tangles / metabolism
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Neurons / metabolism
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Neurons / pathology
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Plasmids / genetics
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / analysis
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Recombinant Fusion Proteins / genetics
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Transfection
Substances
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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Camptothecin