New insights into mechanisms of γ-Diketone-induced axonopathy

Desire Tshala-Katumbay, Paul Desjardins, Mohammad Sabri, Roger Butterworth, Peter Spencer

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We analyzed the impact of axonopathy-inducing agents 1,2-diacetylbenzene (1,2-DAB) and 2,5-hexanedione (2,5-HD) on membrane-bound protein disulfide isomerase (mPDI) versus soluble PDI (sPDI), or PDI-family member thioredoxin (THX), and asked whether changes in PDI/THX were associated with production of oxidative/nitrosative species in the Sprague-Dawley rat. We show that 1,2-DAB and 2,5-HD lower the abundance of sPDI and THX. However, the protein expression of mPDI is increased in 1,2-DAB axonopathy and neuroproteins became more S-nitrosylated. The abundance of heme oxygenase-1 (HO-1) and isoforms of nitric oxide synthase (neuronal, endothelial, and inducible NOS) remained unchanged suggesting that S-nitrosylation occured via increased mPDI-transnitrosylation and/or diminished THX-denitrosylation. The transcription of PDI and glucose regulated protein-78 (GRP-78) remained unchanged indicating that post-translational modifications, e.g. S-nitrosylation, mediate the pathogenesis of γ-diketone axonopathy. These findings open opportunities for new therapeutic testing (e.g., supplementation with denitrosylating THX) in γ-diketone-induced axonal disease.

Original languageEnglish (US)
Pages (from-to)1919-1923
Number of pages5
JournalNeurochemical Research
Volume34
Issue number11
DOIs
StatePublished - Apr 30 2009

Keywords

  • 1,2-Diacetylbenzene
  • 2,5-Hexanedione
  • Giant axonopathy
  • Protein disulfide isomerase
  • S-nitrosylation
  • Thioredoxin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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