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

被引:79
作者
Gasparini, L
Racchi, M
Benussi, L
Curti, D
Binetti, G
Bianchetti, A
Trabucchi, M
Govoni, S
机构
[1] UNIV PAVIA,FAC SCI,INST PHARMACOL,I-27100 PAVIA,ITALY
[2] UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY
关键词
Alzheimer's disease; amyloid precursor protein; COS cells; energy oxidative metabolism; cytochrome c oxidase; sodium azide;
D O I
10.1016/S0304-3940(97)00536-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:113 / 117
页数:5
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