title: Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease.
abstract: Sustained central hypoxia predisposes individuals to dementias such as Alzheimer's disease, in which cells are destroyed in part by disruption of Ca2+ homeostasis. Here, we show that exposure of astrocytes to hypoxia in vitro causes inhibition of plasmalemmal Na+/Ca2+ exchange and excessive mitochondrial Ca2+ loading. Both factors disrupt normal agonist-evoked Ca2+ signalling. Moreover, hypoxia increases the levels of presenilin-1, a major component of a key enzyme involved in Alzheimer's disease. Inhibition of this enzyme partially reverses the effects of hypoxia on Ca2+ signalling. These findings provide an initial cellular basis for understanding the clinical association of hypoxia with Alzheimer's disease.
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK. c.s.peers@leeds.ac.uk
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
authors.forename: Ian F
authors.initials: IF
authors.lastname: Smith
authors.forename: John P
authors.initials: JP
authors.lastname: Boyle
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Pearson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans
chemical_list: D002118:Calcium