[Isomerization of Asp7 increases the toxic effects of amyloid β and its phosphorylated form in SH-SY5Y neuroblastoma cells].
The generation of amyloid β (Aβ) toxic oligomers during the formation of senile plaques and amyloid fibrils is thought to play a central role in the onset and progression of Alzheimer's disease. Aβ production is a physiological process, but the factors that trigger a transition to pathogenic Aβ aggregation remain unknown. Posttranslational modifications of Aβ could potentially induce the transition. The effects of Aβ and its modified forms containing isomerized Asp7, phosphorylated Ser8, or both, were studied in SH-SY5Y human neuroblastoma cells. Asp7 isomerization of was shown to increase cytotoxicity of both the intact and phosphorylated Aβ. An increase in cytotoxicity was not associated with an increased internalization of the isomerized Asp7-containing Aβ or an influence on the function of mitochondria or reduced glutathione and reactive oxygen species levels. The nitric oxide (NO) level was identified as a determinant of the cytotoxic effect of isomerized Asp7-containing peptides, a decrease in NO level correlating with an increase in cytotoxicity.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
E P
EP
Barykin
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
I Yu
IY
Petrushanko
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
K M
KM
Burnysheva
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
A A
AA
Makarov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.|mitkevich@gmail.com.
V A
VA
Mitkevich
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D001224:Aspartic Acid; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001224:Aspartic Acid; D009569:Nitric Oxide
Alzheimer's disease; amyloid β; cytotoxicity; flow cytometry; neuroblastoma; neurodegenerative disorders; nitric oxide; redox status