title: Hypoxia suppresses astrocyte glutamate transport independently of amyloid formation.
abstract: Sustained hypoxia alters the expression of numerous proteins and predisposes individuals to Alzheimer's disease (AD). We have previously shown that hypoxia in vitro alters Ca2+ homeostasis in astrocytes and promotes increased production of amyloid beta peptides (Abeta) of AD. Indeed, alteration of Ca2+ homeostasis requires amyloid formation. Here, we show that electrogenic glutamate uptake by astrocytes is suppressed by hypoxia (1% O2, 24h) in a manner that is independent of amyloid beta peptide formation. Thus, hypoxic suppression of glutamate uptake and expression levels of glutamate transporter proteins EAAT1 and EAAT2 were not mimicked by exogenous application of amyloid beta peptide, or by prevention of endogenous amyloid peptide formation (using inhibitors of either beta or gamma secretase). Thus, dysfunction in glutamate homeostasis in hypoxic conditions is independent of Abeta production, but will likely contribute to neuronal damage and death associated with AD following hypoxic events.
authors.affiliation: School of Medicine, University of Leeds, Worsley Building, Leeds LS2 9JT, UK.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Boycott
authors.forename: Mark
authors.initials: M
authors.lastname: Dallas
authors.forename: John P
authors.initials: JP
authors.lastname: Boyle
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Pearson
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005071:Evoked Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018698:Glutamic Acid