|Title||Hypocapnia induces caspase-3 activation and increases Abeta production.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Xie, Z, Moir, RD, Romano, DM, Tesco, G, Kovacs, DM, Tanzi, RE|
|Keywords||Alzheimer Disease, Amyloid beta-Peptides, Apoptosis, Blotting, Western, Caspase 3, Caspases, Cell Hypoxia, Cell Line, Tumor, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Humans, Hydrogen-Ion Concentration, Hypocapnia, Membrane Proteins, Mutation, Presenilin-1, Transfection|
BACKGROUND: At least half of all cases of early onset (
OBJECTIVE: We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta-protein (Abeta) production, and assessed the influence of the PS1Delta9 FAD mutation on these effects.
METHOD: For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO2
RESULTS: Hypocapnia (20 mm Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1Delta9 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO2) and hypoxia (5%O2) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased Abeta production.
CONCLUSION: The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis.
|Alternate Journal||Neurodegener Dis|
|Grant List||AG/NS, MH 60009-02 / AG / NIA NIH HHS / United States |
K12 AG00294-17 / AG / NIA NIH HHS / United States
P50 AG05134 / AG / NIA NIH HHS / United States
T32 GM07592 / GM / NIGMS NIH HHS / United States