Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells

Laura Gasparini, Marco Racchi, Luisa Benussi, Daniela Curti, Giuliano Binetti, Angelo Bianchetti, Marco Trabucchi, Stefano Govoni

Research output: Contribution to journalArticlepeer-review

Abstract

The present study investigates the influence of energy related metabolic stress on amyloid precursor protein (APP) non-amyloidogenic secretory processing in COS cells. The effect of glucose deprivation on soluble APP (sAPP) secretion has been evaluated: incubation of COS cells with 50 mM 2-deoxy-D-glucose (2-DG) in glucose free medium was able to reduce sAPP secretion (-26%). Sodium azide (NaN3), an inhibitor of cytochrome c oxidase (complex IV of the mitochondrial electron transfer chain) decreased sAPP release in a concentration dependent way (maximum - 75%). Treatment of COS cells with the antioxidant glutathione (GSH) fully antagonized the inhibitory effect of azide (1 mM) and elicited sAPP release over basal level. These results suggest that the inhibition of energy metabolism can influence APP processing leading to a decreased secretion of non-amyloidogenic fragments of APP.

Original languageEnglish
Pages (from-to)113-117
Number of pages5
JournalNeuroscience Letters
Volume231
Issue number2
DOIs
Publication statusPublished - Aug 8 1997

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • COS cells
  • Cytochrome c oxidase
  • Energy oxidative metabolism
  • Sodium azide

ASJC Scopus subject areas

  • Neuroscience(all)

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