Expanded polyglutamine tract itself induces cell death in cultured cells.
Several neurodegenerative diseases including Huntington disease, Machado-Joseph disease and spinocerebellar ataxias type 1 are caused by expansion of a polyglutamine tract within their respective gene products. In order to assess the role of the tract, 293T cells were transfected with plasmids that contain various lengths of CAG repeat encoding polyglutamine without the repeat disorder proteins: (CAG)27, (CAG)40, (CAG)80, (CAG)130, and (CAG)180. Except for (CAG)27, and (CAG)40, 293T cells showed a common set of morphological alterations such as shrinkage, rounding and surface blebbing when the expanded stretch was expressed. In addition, nuclear staining experiments showed chromatin condensation in COS-7 cells transfected with the vectors containing expanded CAG repeats. These results indicate that expanded polyglutamine itself is able to induce cell death, suggesting existence of a common molecular mechanism in the etiology of neurodegenerative polyglutamine diseases.
Bok
K S
KS
Graduate School of Biotechnology, Korea University, Seoul.
Rhim
H
H
Yoo
Y D
YD
Choi
E
E
Ahn
K
K
Kim
I H
IH
Kang
S
S
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D019636:Neurodegenerative Diseases / Q000235:genetics; D010455:Peptides / Q000235:genetics* / Q000502:physiology; D010957:Plasmids / Q000235:genetics*; D013997:Time Factors; D014162:Transfection; D019680:Trinucleotide Repeat Expansion; D001616:beta-Galactosidase / Q000378:metabolism
D010455:Peptides; C019529:polyalanine; C097188:polyglutamine; D001616:beta-Galactosidase