Mutant huntingtin aggregates do not sensitize cells to apoptotic stressors

FEBS Letters

Lesort, Mathieu¹  Chun, Wanjoo¹  Johnson, Gail V.W.¹  Lee, Matthew¹ 

[1]Department of Psychiatry and Behavioral Neurobiology, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, School of Medicine, Birmingham, AL 35294-0017, USA

关键词: Huntington's disease;    Inclusion;    Apoptosis;    Caspase-3;    HD;    Huntington's disease;   

DOI  :  10.1016/S0014-5793(02)02436-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ∼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.

【 授权许可】

Unknown