Role of the proteasome in protein oxidation and neural viability following low-level oxidative stress

Qunxing Ding, Kristi Reinacker, Edgardo Dimayuga, Vidya Nukala, Jennifer Drake, D. Allan Butterfield, Jay C. Dunn, Sarah Martin, Annadora J. Bruce-Keller, Jeffrey N. Keller

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Numerous studies suggest that proteasome inhibition may play a causal role in mediating the increased levels of protein oxidation and neuron death observed in conditions associated with oxidative stress. In the present study we demonstrate that administration of non-toxic levels of oxidative stress does not result in impairment of 20S/26S proteasome activity, and actually increases the expression of specific proteasome subunits. Non-toxic levels of oxidative stress were observed to elevate the amount of protein oxidation in the presence of preserved proteasomal function, suggesting that proteasome inhibition may not mediate increases in protein oxidation following low-level oxidative stress. Preserving basal proteasome function appears to be critical to preventing the neurotoxicity of low-level oxidative stress, based on the ability of proteasome inhibitor treatment to exacerbate oxidative stress toxicity. Taken together, these data indicate that maintaining neural proteasome function may be critical to preventing neurotoxicity, but not the increase in protein oxidation, following low-level oxidative stress.

Original languageEnglish
Pages (from-to)228-232
Number of pages5
JournalFEBS Letters
Volume546
Issue number2-3
DOIs
StatePublished - Jul 10 2003

Bibliographical note

Funding Information:
This work was supported by the American Heart Association (J.N.K.), and grants from the National Institutes of Health (AG018437, AG005119, J.N.K.). The authors wish to thank Dr. William R. Markesbery for his continual support.

Keywords

  • Neuron
  • Neurotoxicity
  • Oxidative stress
  • Proteasome
  • Protein oxidation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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