Enhanced BK-induced calcium responsiveness in PC12 cells expressing the C100 fragment of the amyloid precursor protein.
Several lines of evidence have implicated the amyloid precursor protein (APP) and its metabolic products as key players in Alzheimer's disease (AD) pathophysiology. The approximately 100 amino acid C-terminal fragment (C100) of APP has been shown to accumulate intracellularly in neurons expressing familial AD (FAD) mutants of APP and to cause neurodegeneration when expressed in transfected neuronal cells. Transgenic animals expressing this fragment in the brain also exhibit some neuropathological and behavioral AD-like deficits. Here, we present evidence that PC12 cells expressing the C100 fragment either via stable transfections or herpes simplex virus-mediated infections show alterations in calcium handling that are similar to those previously shown in fibroblasts from AD patients. This alteration in calcium homeostasis may contribute to the deleterious effects of C100 in PC12 cells. Our data also lend support for a pathophysiological role for C100 since it induces an alteration thought to play an important role in AD pathology.
Pascale
A
A
Laboratory of Applied Neuroscience, Institute for Cognitive and Computational Sciences, Georgetown University Medical Center, The Research Bldg., Room WP 14, 3970 Reservoir Rd., NW, Washington, DC, USA.
Bhagavan
S
S
Nelson
T J
TJ
Neve
R L
RL
McPhie
D L
DL
Etcheberrigaray
R
R
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D018139:Simplexvirus / Q000235:genetics; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; C092826:amyloid precursor protein, carboxy-terminal 100 residues; D001920:Bradykinin