Frataxin deficiency induces Schwann cell inflammation and death

Chunye Lu, Robert Schoenfeld, Yuxi Shan, Hsing Jo Tsai, Bruce Hammock, Gino A Cortopassi

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1052-1061
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1792
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Schwann Cells
Cell Death
Inflammation
Spinal Ganglia
Cell Line
Friedreich Ataxia
frataxin
Oligodendroglia
Demyelinating Diseases
Pharmaceutical Preparations
Genes
Interleukin-6
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Cell Proliferation
Neurons
Messenger RNA
Mutation

Keywords

  • Dorsal root ganglia (DRG) neuron
  • Frataxin
  • Friedreich's ataxia (FRDA)
  • Inflammatory response
  • Schwann cells
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Medicine(all)

Cite this

Frataxin deficiency induces Schwann cell inflammation and death. / Lu, Chunye; Schoenfeld, Robert; Shan, Yuxi; Tsai, Hsing Jo; Hammock, Bruce; Cortopassi, Gino A.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1792, No. 11, 11.2009, p. 1052-1061.

Research output: Contribution to journalArticle

Lu, Chunye ; Schoenfeld, Robert ; Shan, Yuxi ; Tsai, Hsing Jo ; Hammock, Bruce ; Cortopassi, Gino A. / Frataxin deficiency induces Schwann cell inflammation and death. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2009 ; Vol. 1792, No. 11. pp. 1052-1061.
@article{34c9d9e406704b11bfd9c5a839ee72d9,
title = "Frataxin deficiency induces Schwann cell inflammation and death",
abstract = "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.",
keywords = "Dorsal root ganglia (DRG) neuron, Frataxin, Friedreich's ataxia (FRDA), Inflammatory response, Schwann cells, siRNA",
author = "Chunye Lu and Robert Schoenfeld and Yuxi Shan and Tsai, {Hsing Jo} and Bruce Hammock and Cortopassi, {Gino A}",
year = "2009",
month = "11",
doi = "10.1016/j.bbadis.2009.07.011",
language = "English (US)",
volume = "1792",
pages = "1052--1061",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "11",

}

TY - JOUR

T1 - Frataxin deficiency induces Schwann cell inflammation and death

AU - Lu, Chunye

AU - Schoenfeld, Robert

AU - Shan, Yuxi

AU - Tsai, Hsing Jo

AU - Hammock, Bruce

AU - Cortopassi, Gino A

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

KW - Dorsal root ganglia (DRG) neuron

KW - Frataxin

KW - Friedreich's ataxia (FRDA)

KW - Inflammatory response

KW - Schwann cells

KW - siRNA

UR - http://www.scopus.com/inward/record.url?scp=73349107807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349107807&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2009.07.011

DO - 10.1016/j.bbadis.2009.07.011

M3 - Article

C2 - 19679182

AN - SCOPUS:73349107807

VL - 1792

SP - 1052

EP - 1061

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 11

ER -