Document Detail

Heat shock protein 70 alters the endosome-lysosomal localization of huntingtin.
MedLine Citation:
PMID:  17334227     Owner:  NLM     Status:  MEDLINE    
Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)(100)] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immunocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)(18)] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome-lysosomal accumulation, from a "dispersed vacuole (DV)" type into a coalescent "perinuclear vacuole (PV)" type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome- lysosomal system, and that this contributes to huntingtin proteolysis.
Bong Sun Kang; Jin-Young Ahn; Min Ky Kim; Hyun-Jeong Kim; Lami Kang; Hun-Chang Lim; Kyung-Sook Park; Jae-Seon Lee; Jeong-Sun Seo; Choong Ik Cha; Seung U Kim; Yoon Jeong Park; Manho Kim
Related Documents :
9245737 - Increased transcript level of rbm3, a member of the glycine-rich rna-binding protein fa...
14982777 - Geldanamycin, a ligand of heat shock protein 90, inhibits the replication of herpes sim...
17613377 - The influence of attachment to beef surfaces on the survival of cells of salmonella ent...
14766677 - Role of cyclooxygenase in ventricular effects of adrenomedullin: is adrenomedullin a do...
10704477 - Higher levels of organization in the interphase nucleus of cycling and differentiated c...
18487027 - Comparison of activated caspase detection methods in the gentamicin-treated chick cochlea.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental & molecular medicine     Volume:  39     ISSN:  1226-3613     ISO Abbreviation:  Exp. Mol. Med.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-03-05     Completed Date:  2007-03-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607880     Medline TA:  Exp Mol Med     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  38-46     Citation Subset:  IM    
Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Survival
Cytoplasm / metabolism
Endosomes / metabolism*
HSP70 Heat-Shock Proteins / genetics,  metabolism*
Lysosomes / metabolism*
NIH 3T3 Cells
Nerve Tissue Proteins / genetics,  metabolism*
Nuclear Proteins / genetics,  metabolism*
Peptide Hydrolases / metabolism
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; EC 3.4.-/Peptide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expres...
Next Document:  Psammaplin A is a natural prodrug that inhibits class I histone deacetylase.