Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease.
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.
Peers
Chris
C
School of Medicine, University of Leeds, Leeds LS2 9JT, UK. c.s.peers@leeds.ac.uk
Smith
Ian F
IF
Boyle
John P
JP
Pearson
Hugh A
HA
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
D002118:Calcium