Document Detail


Frataxin deficiency induces Schwann cell inflammation and death.
MedLine Citation:
PMID:  19679182     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in the frataxin gene cause dorsal root ganglion demyelination and neurodegeneration, which leads to Friedreich's ataxia. However the consequences of frataxin depletion have not been measured in dorsal root ganglia or Schwann cells. We knocked down frataxin in several neural cell lines, including two dorsal root ganglia neural lines, 2 neuronal lines, a human oligodendroglial line (HOG) and multiple Schwann cell lines and measured cell death and proliferation. Only Schwann cells demonstrated a significant decrease in viability. In addition to the death of Schwann cells, frataxin decreased proliferation in Schwann, oligodendroglia, and slightly in one neural cell line. Thus the most severe effects of frataxin deficiency were on Schwann cells, which enwrap dorsal root ganglia neurons. Microarray of frataxin-deficient Schwann cells demonstrated strong activations of inflammatory and cell death genes including interleukin-6 and Tumor Necrosis Factor which were confirmed at the mRNA and protein levels. Frataxin knockdown in Schwann cells also specifically induced inflammatory arachidonate metabolites. Anti-inflammatory and anti-apoptotic drugs significantly rescued frataxin-dependent Schwann cell toxicity. Thus, frataxin deficiency triggers inflammatory changes and death of Schwann cells that is inhibitable by inflammatory and anti-apoptotic drugs.
Authors:
Chunye Lu; Robert Schoenfeld; Yuxi Shan; Hsing-Jo Tsai; Bruce Hammock; Gino Cortopassi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-08-10
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1792     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-19     Completed Date:  2009-12-23     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1052-61     Citation Subset:  IM    
Affiliation:
Department of Molecular Biosciences, University of California, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Death / genetics
Cell Line
Cell Survival
Ganglia, Spinal / metabolism*,  pathology
Gene Knockdown Techniques
Heredodegenerative Disorders, Nervous System / genetics,  metabolism*,  pathology
Humans
Inflammation / genetics,  metabolism,  pathology
Interleukin-6 / genetics,  metabolism
Iron-Binding Proteins*
Mutation*
Neurons / metabolism*,  pathology
Schwann Cells
Grant Support
ID/Acronym/Agency:
AG11967/AG/NIA NIH HHS; AG16719/AG/NIA NIH HHS; AG23311/AG/NIA NIH HHS; ES002710/ES/NIEHS NIH HHS; ES00469/ES/NIEHS NIH HHS; EY12245/EY/NEI NIH HHS; P42 ES004699/ES/NIEHS NIH HHS; R01 ES002710/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/IL6 protein, human; 0/Interleukin-6; 0/Iron-Binding Proteins; 0/frataxin
Comments/Corrections

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