Recombinant human erythropoietin reduces aggregation of mutant Cu/Zn-binding superoxide dismutase (SOD1) in NSC-34 cells

Neurosci Lett. 2011 Oct 24;504(2):107-111. doi: 10.1016/j.neulet.2011.09.008. Epub 2011 Sep 16.


Human erythropoietin (hEPO) has multiple actions in non-hematopoietic tissues, including neurotrophic, anti-oxidant, anti-apoptotic, and anti-inflammatory effects. To examine the effect of EPO in an vitro model of amyotrophic lateral sclerosis (ALS), we stably overexpressed wild SOD1 and a mutant form, SOD1/G93A, in NSC-34 motoneuron-like cells. Transformants harboring the wild and mutant forms of SOD1 were selected by G418 selection and immunoblot analysis. RT-PCR analysis showed that cox-2 expression was increased in the NSC-34/mSOD1s, and MTT assays and BrdU-ELISAs revealed reduced cell growth and proliferation in the NSC-34/mSOD1 cell line. Incubation with 5 or 10IU/mL rhEPO increased the viability and decreased the cox-2 expression in the dNSC-34/mSOD1s cells. Immunocytochemical staining with anti-SOD1 antibody revealed the presence of aggregates of mSOD1 protein in dNSC-34/mSOD1 cells. Incubation with10IU/mL rhEPO reduced the proportion of cells containing such aggregates. Our findings suggest that the anti-oxidant and anti-inflammatory effects of EPO increase the survival of NSC-34/mSOD1 cells and reduce aggregation of the mutant SOD1 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Bromodeoxyuridine
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Cyclooxygenase 2 / biosynthesis
  • DNA, Complementary / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Erythropoietin / pharmacology*
  • Humans
  • Immunohistochemistry
  • Mice
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Mutagenesis
  • Mutation
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Plasmids / genetics
  • RNA / biosynthesis
  • RNA / genetics
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / pharmacology
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism*


  • Antimetabolites
  • DNA, Complementary
  • Oligonucleotides
  • Recombinant Proteins
  • Erythropoietin
  • RNA
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Choline O-Acetyltransferase
  • Bromodeoxyuridine