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.
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Transient osmotic stress facilitates mutant huntingtin aggregation.
Neuroreport
December 2002
Department of Psychiatry and Behavioral Neurobiology, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Human neuroblastoma SH-SY5Y cell lines stably expressing mutant truncated huntingtin with 82 (mutant) glutamine repeats (N63-82Q) were briefly exposed to hyperosmotic conditions which decrease cell volume and therefore transiently increased the concentration of N63-82Q, as well as activating specific stress-induced pathways. Transient hyperosmotic treatment significantly increased the number of cells with aggregates. When the N63-82Q cells were subsequently returned to iso-osmotic medium after the treatment, the number of cells with aggregates remained constant up to 12 h.
View Article and Find Full Text PDFMutant huntingtin aggregates do not sensitize cells to apoptotic stressors.
FEBS Lett
March 2002
Department of Psychiatry and Behavioral Neurobiology, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, School of Medicine, Birmingham, AL 35294-0017, USA.
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.
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