title: Mutant huntingtin aggregates do not sensitize cells to apoptotic stressors.
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.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, School of Medicine, Birmingham, AL 35294-0017, USA.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lesort
authors.forename: Matthew
authors.initials: M
authors.lastname: Lee
authors.forename: Gail V W
authors.initials: GV
authors.lastname: Johnson
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology; D015151:Immunoblotting; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D009994:Osmolar Concentration; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D019076:Transgenes; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; C086055:HTT protein, human; D000071058:Huntingtin Protein; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013012:Sorbitol; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine