Premium
Hypoxic remodelling of Ca 2+ mobilization in type I cortical astrocytes: involvement of ROS and pro‐amyloidogenic APP processing
Author(s) -
Smith Ian F.,
Boyle John P.,
Green Kim N.,
Pearson Hugh A.,
Peers Chris
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02212.x
Subject(s) - hypoxia (environmental) , endocrinology , medicine , homeostasis , reactive oxygen species , chemistry , amyloid precursor protein , amyloid beta , western blot , biology , microbiology and biotechnology , alzheimer's disease , biochemistry , oxygen , peptide , disease , organic chemistry , gene
Chronic hypoxia (CH) alters Ca 2+ homeostasis in various cells and may contribute to disturbed Ca 2+ homeostasis of Alzheimer's disease. Here, we have employed microfluorimetric measurements of [Ca 2+ ] i to investigate the mechanism underlying augmentation of Ca 2+ signalling by chronic hypoxia in type I cortical astrocytes. Application of bradykinin evoked significantly larger rises of [Ca 2+ ] i in hypoxic cells as compared with control cells. This augmentation was prevented fully by either melatonin (150 µ m ) or ascorbic acid (200 µ m ), indicating the involvement of reactive oxygen species. Given the association between hypoxia and increased production of amyloid β peptides (AβPs) of Alzheimer's disease, we performed immunofluorescence studies to show that hypoxia caused a marked and consistent increased staining for AβPs and presenilin‐1 (PS‐1). Western blot experiments also confirmed that hypoxia increased PS‐1 protein levels. Hypoxic increases of AβP production was prevented with inhibitors of either γ‐ or β‐secretase. These inhibitors also partially prevented the augmentation of Ca 2+ signalling in astrocytes. Our results indicate that chronic hypoxia enhances agonist‐evoked rises of [Ca 2+ ] i in cortical astrocytes, and that this can be prevented by antioxidants and appears to be associated with increased AβP formation.