Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurochem. 2012 May;121(4):639-48. doi: 10.1111/j.1471-4159.2012.07711.x. Epub 2012 Mar 28.

Activation of Elk-1 participates as a neuroprotective compensatory mechanism in models of Huntington's disease.

Author information

1
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.

Abstract

The transcription factor Elk-1 has been revealed as neuroprotective against toxic stimuli. In this study, we explored the neuroprotective capacity of Elk-1 in Huntington's disease. To this aim, we used two exon-1 mutant huntingtin (mhtt) mouse models (R6/1 and R6/2), and a full-length mhtt striatal cell model (STHdh(Q111/Q111) ). Analysis of Elk-1 and pElk-1(Ser383) in the striatum of R6 mice revealed increased levels during the disease progression. Similarly, Elk-1 and pElk-1(Ser383) levels were increased in STHdh(Q111/Q111) cells when compared with wild-type cells. In addition, we observed a predominant nuclear localization of Elk-1 in STHdh(Q111/Q111) cells, and in the striatum of 30-week-old R6/1 mice. Nuclear Elk-1 did not colocalize with mhtt aggregates, suggesting a higher transcriptional activity. In agreement, the knock-down of Elk-1 decreased immediate early genes expression in STHdh(Q111/Q111) cells, but not in wild-type cells. Interestingly, reduction of Elk-1 levels by siRNAs transfection promoted cell death and caspase 3 cleavage in STHdh(Q111/Q111) cells, but not in wild-type cells. In summary, we propose that increased protein levels, phosphorylation and nuclear localization of Elk-1 observed in exon-1 and full-length Huntington's disease models could be a compensatory mechanism activated by striatal cells in response to the presence of mhtt that contributes to neuroprotection.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center