Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

We show that A␤-resistant PC12 cell lines exhibit increased expression of multiple Prx isoforms with reduced cysteine oxidation

Robert C. Cumming; Richard Dargusch; Wolfgang H. Fischer; David Schubert


Scholarcy highlights

  • Common form of dementia in the elderly, is characterized by extracellular neuritic plaques containing the amyloid beta peptide1–42 and intracellular neurofibrillary tangles composed mainly of hyperphosphorylated tau protein
  • When PC12 cells were transiently exposed to 10 ␮M A␤1–42, the same group of enzymes was up-regulated including triosephosphate isomerase, phosphoglycerate mutase, ␣-enolase, and aldolase A
  • Because multiple proteins can reside in the same spot and mask the relative protein abundance of Prx isoforms on silver-stained two-dimensional gels, we examined expression levels of all six Prx isoforms in lysates from both parental and A␤-resistant PC12 cell lines by immunoblotting with isoform-specific antibodies
  • Rat primary hippocampal neurons transfected with wild type Prx1 exhibit resistance to A␤, whereas the cysteine mutant confers no protection. These results indicate that increased expression of Prx1 can confer resistance to A␤ toxicity that is dependent on a functional catalytic cysteine residue within the protein
  • Initial studies of PC12 clonal cell lines selected for resistance to A␤
  • Averaging of the densitometric values for the Prx-SO2–3-specific bands revealed no significant difference between control and Alzheimer disease brain sets
  • An acidic a previous study, decreased Trx and increased thioredoxin reductase levels were spot appeared beside the main Prx2 spot in the AD, Down syn- found in the amygdala and hippocampus regions of AD patients drome, and Parkinson disease samples but not in the controls compared with control patients
  • In support of our findings, immunoblot analysis of cortex homogenates revealed no significant difference in Trx protein levels between Alzheimer disease and control brains, suggesting that the increased number of glial cells in AD brains masks the reduction in neuronal Trx1 when brain homogenates are analyzed

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