EFFECT OF ENERGY-SHORTAGE AND OXIDATIVE STRESS ON AMYLOID PRECURSOR PROTEIN-METABOLISM IN COS CELLS

The present study investigates the influence of energy related metabol ic stress on amyloid precursor protein (APP) non-amyloidogenic secreto ry processing in COS cells. The effect of glucose deprivation on solub le APP (sAPP) secretion has been evaluated: incubation of COS cells wi th 50 mM 2-deoxy-D-glucose (2-DG) in glucose free medium was able to r educe sAPP secretion (-26%). Sodium azide (NaN3), an inhibitor of cyto chrome c oxidase (complex IV of the mitochondrial electron transfer ch ain) decreased sAPP release in a concentration dependent way (maximum -75%). Treatment of COS cells with the antioxidant glutathione (GSH) f ully antagonized the inhibitory effect of azide (1 mM) and elicited sA PP release over basal level. These results suggest that the inhibition of energy metabolism can influence APP processing leading to a decrea sed secretion of non-amyloidogenic fragments of APP. (C) 1997 Elsevier Science Ireland Ltd.