| First Author | Zourlidou A | Year | 2007 |
| Journal | Hum Mol Genet | Volume | 16 |
| Issue | 9 | Pages | 1078-90 |
| PubMed ID | 17360721 | Mgi Jnum | J:121760 |
| Mgi Id | MGI:3711590 | Doi | 10.1093/hmg/ddm057 |
| Citation | Zourlidou A, et al. (2007) Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation. Hum Mol Genet 16(9):1078-90 |
| abstractText | Huntington's disease (HD) is caused by an expanded polyglutamine tract in the huntingtin protein. Mitochondrial dysfunction and free radical damage occur in both R6/2 mice and HD patient brains and might play a role in disease pathogenesis. In cell culture systems, heat-shock protein 27 (Hsp27), a small molecular chaperone, suppresses mutant huntingtin-induced reactive oxygen species formation and cell death. To investigate this in vivo, we conducted an extensive phenotypic characterization of mice arising from a cross between R6/2 mice and Hsp27 transgenic mice but did not observe an improvement of the R6/2 phenotype. Hsp27 overexpression had no effect in reducing oxidative stress in the R6/2 brain, assessed by measuring striatal aconitase activity and protein carbonylation levels. Native protein gel analysis revealed that transgenic Hsp27 forms active, large oligomeric species in heat-shocked brain lysates, demonstrating that it is efficiently activated upon stress. In contrast, Hsp27 in double transgenic brains exists predominantly as a low molecular weight, inactive species. This suggests that Hsp27, which is otherwise activatable upon heat shock, remains inactive in the R6/2 model of chronic neurodegeneration. Hsp27 transgenics had been previously shown to be protected from acute stresses such as kainate administration, ischemia/reperfusion heart injury and neonatal nerve injury. Our study is the first to suggest a differential modulation of Hsp27 activation in vivo and, importantly, it illustrates the diverse effect of Hsp27 on acute versus chronic models of disease. |
