Wild type but not mutant APP is involved in protective adaptive responses against oxidants

被引:10
作者
Cenini, Giovanna [1 ,3 ]
Maccarinelli, Giuseppina [1 ]
Lanni, Cristina [2 ]
Bonini, Sara Anna [1 ]
Ferrari-Toninelli, Giulia [1 ]
Govoni, Stefano [2 ]
Racchi, Marco [2 ]
Butterfield, David Allan [3 ]
Memo, Maurizio [1 ,4 ]
Uberti, Daniela [1 ]
机构
[1] Univ Brescia, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy
[2] Univ Pavia, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy
[3] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA
[4] Univ Turin, Natl Inst Neurosci, Turin, Italy
关键词
APP; p53; Oxidative stress; SOD; Cell vulnerability; Adaptive response; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE BRAIN; IMPAIR SYNAPTIC PLASTICITY; MILD COGNITIVE IMPAIRMENT; SEQUENCE-SPECIFIC DNA; OXIDATIVE STRESS; BETA-PEPTIDE; LIPID-PEROXIDATION; FREE-RADICALS; NITRATED PROTEINS;
D O I
10.1007/s00726-009-0438-1
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
This study points out different behaviour between HEK cells overexpressing wild-type or mutant APP when exposed to oxidative insult. Although apparently both APPwt and APPmut overexpression conferred resistance to oxidative insult, some differences in terms of degree of protection was observed in the two clones. We found that the two clones differed, especially, in terms of redox profile. HEK-APPmut cells were characterized by higher levels of oxidative markers in comparison with HEK-APPwt. In addition, SOD activity appeared more efficient in HEK-APPwt than in HEK-APPmut, thus justifying the differences in terms of cell survival in the two clones. We suggest that, according to "hormesis theory", in HEK-APPwt cells low amount of oxidative stress can exert a beneficial effect that at a higher intensity results harmful. In contrast, HEK-APPmut cells lost this stress resistance probably because the degree of oxidative stress is too high and the antioxidant enzymes are themselves compromised.
引用
收藏
页码:271 / 283
页数:13
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