Amyloid-beta induced cell death is independent of free radicals.
Acutely dissociated rat cerebellar granule cell neurons were incubated with amyloid-beta (1-42) and studied by flow cytometry. Amyloid-beta caused a dose-dependent loss of viability, as determined by intracellular accumulation of propidium iodide (PI),and that was not accompanied by significant elevation of intracellular calcium, measured by Fluo-3 or reactive oxygen species (ROS), measured by 2',7'-dihydro-dichlorfluorescein diacetate (DCF). Carnosine, a ROS scavenger and an inhibitor of non-enzymatic glycosylation, partially reduced cell death caused by amyloid-beta. We conclude that amyloid-beta causes a relatively acute loss of cell viability in cerebellar granule cell neurons, which does not result from either elevation of intracellular calcium concentration or generation of ROS.
Boldyrev
Alexander
A
International Biotechnological Center, M.V. Lomonosov Moscow State University, Department of Biochemistry, 119992 Moscow, Russia. aaboldyrev@mail.ru
Koudinov
Alexey
A
Berezov
Temirboulat
T
Carpenter
David O
DO
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002336:Carnosine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism*; D007202:Indicators and Reagents; D042541:Intracellular Space / Q000187:drug effects; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011419:Propidium; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014966:Xanthenes
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005456:Fluorescent Dyes; D005609:Free Radicals; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D014966:Xanthenes; C059715:Fluo-3; D011419:Propidium; D016202:N-Methylaspartate; D002336:Carnosine; D007608:Kainic Acid; D002118:Calcium