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.

Medienart:

Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:50

Enthalten in:

Molekuliarnaia biologiia - 50(2016), 5 vom: 10. Sept., Seite 863-869

Sprache:

Russisch

Beteiligte Personen:

Barykin, E P [VerfasserIn]
Petrushanko, I Yu [VerfasserIn]
Burnysheva, K M [VerfasserIn]
Makarov, A A [VerfasserIn]
Mitkevich, V A [VerfasserIn]

Themen:

30KYC7MIAI
31C4KY9ESH
Alzheimer's disease
Amyloid β
Amyloid beta-Peptides
Aspartic Acid
Cytotoxicity
Flow cytometry
Journal Article
Neuroblastoma
Neurodegenerative disorders
Nitric Oxide
Nitric oxide
Redox status

Anmerkungen:

Date Completed 21.03.2017

Date Revised 21.03.2017

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM266077188