The ubiquitin/proteasome pathway:: friend or foe in zinc-, cadmium-, and H2O2-induced neuronal oxidative stress

被引:51
作者
Figueiredo-Pereira, ME
Cohen, G
机构
[1] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA
[2] CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA
关键词
cadmium; hydrogen peroxide; oxidative stress; ubiquitin pathway; zinc;
D O I
10.1023/A:1006909918866
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
One of the hallmarks of neurodegeneration is the accumulation of ubiquitinated proteins in intraneuronal inclusions in the cytosol, endosomes/lysosomes and nuclei of affected cells. The relationship between inclusion production and cell viability is not well understood. On the one hand inclusions may be beneficial and result from an attempt of the cell to isolate a subclass of ubiquitinated proteins that are not effectively degraded. On the other hand, the inclusions may impede normal cell function contributing to cell death. To address this issue we treated mouse neuronal HT4 cells with three toxic agents cadmium, zinc and H2O2, and investigated their effects on glutathione homeostasis, on accumulation of ubiquitinated proteins and on cell viability. The three treatments induce oxidative stress manifested by decreases in glutathione (GSH) and/or increases in protein mixed disulfides (PrSSG). After an overnight recovery period in the absence of treatment, GSH and PrSSG were restored to almost normal levels. However, the levels of ubiquitinated proteins were significantly increased, and cell viability was sharply reduced. These results suggest that the ubiquitin-proteasome pathway is recruited for removal of proteins that are oxidatively modified. However, if the ubiquitinated proteins are not efficiently degraded, they accumulate in the cell and contribute to a decrease in cell viability.
引用
收藏
页码:65 / 69
页数:5
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