Amyloid beta peptides mediate hypoxic augmentation of Ca(2+) channels.
Clinical studies indicate that neurodegeneration caused by Alzheimer's amyloid beta peptide (AbetaP) formation can be triggered or induced by prolonged (chronic) hypoxia. Here, we demonstrate that 24-h culture of PC12 cells in 10% O(2) leads to induction of a Cd(2+)-resistant Ca(2+) influx pathway and selective potentiation of L-type Ca(2+) current. Both effects were suppressed or prevented by a monoclonal antibody raised against the N'-terminus of AbetaP, and were fully mimicked by AbetaP(1-40 and) AbetaP(1-42), but not by AbetaP(40-1). Potentiation of L-type currents was also induced by exposure to AbetaP(25-35). Our results indicate that hypoxia induces enhancement of Ca(2+) channels, which is mediated by increased AbetaP formation.
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Institute for Cardiovascular Research, University of Leeds, Leeds, UK.
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D016229:Amyloid beta-Peptides / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D015687:Cell Hypoxia; D004351:Drug Resistance; D004357:Drug Synergism; D004553:Electric Conductivity; D010100:Oxygen / Q000008:administration & dosage; D016716:PC12 Cells; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010446:Peptide Fragments; D002104:Cadmium; D010100:Oxygen; D002118:Calcium