PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide.
Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Abeta, a 39-43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes Abeta. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H(2)O(2), rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H(2)O(2) in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerability to A23187, and decreased vulnerability to H(2)O(2).
McKeon-O'Malley
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Massachusetts General Hospital and Harvard University, Genetics and Aging Unit, 149 13th Street, Charlestown, MA, USA. omalley@helix.mgh.harvard.edu
Wells
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J
Fine
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Ullman
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MD
Volicer
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D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004351:Drug Resistance; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D007476:Ionophores; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C092826:amyloid precursor protein, carboxy-terminal 100 residues; D000001:Calcimycin; D006861:Hydrogen Peroxide; D002118:Calcium