Document Detail


Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells.
MedLine Citation:
PMID:  18514418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alpha-synuclein (alpha-syn) is implicated in the pathogenesis of Parkinson's disease (PD). Mutations in alpha-syn gene or alpha-syn locus (SNCA) triplication are associated with mitochondrial abnormalities and early onset of familial PD. The goals of the present study were to examine whether alpha-syn is localized in the mitochondria of alpha-syn overexpressing cells (HEK-syn cells); and whether alpha-syn overexpression causes cells to be more vulnerable to mitochondrial toxin, rotenone. Western blotting and confocal microscopy techniques were employed to assess localization of alpha-syn in the mitochondria of HEK-293 cells that were stably transfected with human wild-type alpha-syn. The results demonstrated that the mitochondrial fractions that were isolated from HEK-syn cells showed the presence of alpha-syn, whereas, no alpha-syn was detected in the mitochondrial fractions of control HEK cells. The mitochondria of HEK-syn cells were found to be more susceptible to rotenone-induced toxicity when compared to control HEK cells. The intracellular ATP levels were significantly decreased in HEK-syn cells in response to sub toxic concentrations of rotenone. These results suggest that under overexpression conditions, alpha-syn may translocate to mitochondria and cause enhanced toxicity in response to sub toxic concentrations of mitochondrial toxins. This study has implications to the pathogenesis of familial PD where alpha-syn overexpression is mainly involved.
Authors:
Shaik Shavali; Holly M Brown-Borg; Manuchair Ebadi; James Porter
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Publication Detail:
Type:  Journal Article     Date:  2008-05-08
Journal Detail:
Title:  Neuroscience letters     Volume:  439     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-10     Completed Date:  2008-10-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  125-8     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of North Dakota, School of Medicine and Health Sciences, 501 North Columbia Road,Grand Forks, ND 58202, USA. sshavali@medicine.nodak.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Analysis of Variance
Cell Line, Transformed
Cyclooxygenase 1 / metabolism
Dose-Response Relationship, Drug
Gene Expression / drug effects,  physiology*
Humans
Insecticides / pharmacology
Microscopy, Confocal / methods
Mitochondria / metabolism*
Rotenone / pharmacology
Transfection / methods
alpha-Synuclein / metabolism*
Grant Support
ID/Acronym/Agency:
R01 AG017059-04/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Insecticides; 0/alpha-Synuclein; 56-65-5/Adenosine Triphosphate; 83-79-4/Rotenone; EC 1.14.99.1/Cyclooxygenase 1
Comments/Corrections

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