Abstract
It has been postulated that neuronal inclusions composed of mutant huntingtin may play a causative role in the pathogenesis of Huntington's disease. To study the putative role of aggregates in modulating apoptotic vulnerability, SH-SY5Y cell lines stably expressing truncated huntingtin with 18 (wild-type) (N63-18Q) or 82 (mutant) (N63-82Q) glutamine repeats were established. Aggregates were observed in approximately 13% of the N63-82Q cells; no aggregates were observed in the N63-18Q cells. In response to apoptotic stimuli such as staurosporine or hyperosmotic stress, caspase-3 activity was significantly greater in the N63-82Q cells compared to the N63-18Q cells. However, double immunostaining for huntingtin and active caspase-3 revealed that the presence of aggregates did not correlate with the presence of active caspase-3, indicating that aggregates do not contribute to the increase in apoptosis in the N63-82Q cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis* / drug effects
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Caspase 3
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Caspases / metabolism
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Humans
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Huntingtin Protein
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Huntington Disease / etiology
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Immunoblotting
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Macromolecular Substances
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / pharmacology
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Neuroblastoma / drug therapy
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Nuclear Proteins / pharmacology
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Osmolar Concentration
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Poly(ADP-ribose) Polymerases / metabolism
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Sorbitol / pharmacology
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Staurosporine / pharmacology
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Transgenes
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Trinucleotide Repeat Expansion / genetics
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Tumor Cells, Cultured
Substances
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Enzyme Inhibitors
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HTT protein, human
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Huntingtin Protein
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Macromolecular Substances
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Nerve Tissue Proteins
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Nuclear Proteins
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Sorbitol
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Poly(ADP-ribose) Polymerases
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CASP3 protein, human
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Caspase 3
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Caspases
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Staurosporine