title: The effects of endogenous non-peptide molecule isatin and hydrogen peroxide on proteomic profiling of rat brain amyloid-β binding proteins: relevance to Alzheimer's disease?
abstract: The amyloid-β peptide is considered as a key player in the development and progression of Alzheimer's disease (AD). Although good evidence exists that amyloid-β accumulates inside cells, intracellular brain amyloid-binding proteins remain poorly characterized. Proteomic profiling of rat brain homogenates, performed in this study, resulted in identification of 89 individual intracellular amyloid-binding proteins, and approximately 25% of them were proteins that we had previously identified as specifically binding to isatin, an endogenous neuroprotector molecule. A significant proportion of the amyloid-binding proteins (more than 30%) are differentially expressed or altered/oxidatively modified in AD patients. Incubation of brain homogenates with 70 µM hydrogen peroxide significantly influenced the profile of amyloid-β binding proteins and 0.1 mM isatin decreased the number of identified amyloid-β binding proteins both in control and hydrogen peroxide treated brain homogenates. The effects of hydrogen peroxide and isatin have been confirmed in optical biosensor experiments with purified glyceraldehyde-3-phosphate dehydrogenase, one of the known crucial amyloid-β binding proteins (also identified in this study). Data obtained suggest that isatin protects crucial intracellular protein targets against amyloid binding, and possibly favors intracellular degradation of this protein via preventing formation of amyloid-β oligomers described in the literature for some isatin derivatives.
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. professor57@yandex.ru.
authors.forename: Alexei E
authors.initials: AE
authors.lastname: Medvedev
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. olbun@yandex.ru.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Buneeva
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. a.t.kopylov@gmail.com.
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Kopylov
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. oksana_gnedenko@pochta.ru.
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Gnedenko
authors.affiliation: School of Biology, Lomonosov Moscow State University, Moscow 119191, Russia. marmed64@yandex.ru.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Medvedeva
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. kozinsa@gmail.com.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozin
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. asi@icnet.ru.
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Ivanov
authors.affiliation: Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, Moscow 119121, Russia. vic@ibmh.msk.su.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Zgoda
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. aamakarov@eimb.ru.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Makarov
mesh_terms: D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007510:Isatin / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics; D051381:Rats
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D007510:Isatin; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases