Wild type but not mutant APP is involved in protective adaptive responses against oxidants.
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.
Cenini
Giovanna
G
Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
Maccarinelli
Giuseppina
G
Lanni
Cristina
C
Bonini
Sara Anna
SA
Ferrari-Toninelli
Giulia
G
Govoni
Stefano
S
Racchi
Marco
M
Butterfield
David Allan
DA
Memo
Maurizio
M
Uberti
Daniela
D
D000222:Adaptation, Physiological; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D009154:Mutation / Q000235:genetics; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D016877:Oxidants; D058255:Protease Nexins; D011956:Receptors, Cell Surface