Propagation of intercellular calcium waves in PC12 cells overexpressing a carboxy-terminal fragment of amyloid precursor protein.
We have recently found that PC12 cells overexpressing a C-terminal 97 amino acid fragment containing the beta/A4 amyloid peptide of amyloid precursor protein (APP) exhibit an induced production of the gap junctional protein connexin43 (Cx43) and an induction of gap junctional communication as assessed by dye-transfer. In studies of two beta/A4-transfected PC12 clones, we show here that these cells, unlike normal PC12 cells or those transfected with vector alone, have the capacity for intercellular transmission of calcium waves as determined by imaging of calcium with fura-2. Intercellular wave propagation occurred in the absence of extracellular calcium and was blocked by known inhibitors of gap junctional communication (octanol and 12-O-tetradecanoyl-phorbol-13-acetate), suggesting mediation by gap junctions. The results indicate a disruptive influence of the C-terminal region of APP or of beta/A4 amyloid peptide on intercellular signaling via gap junctions, which may be relevant to the normal functions of APP or to pathology in Alzheimer's disease.
Lynn
B D
BD
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Marotta
C A
CA
Nagy
J I
JI
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism; D016257:Fura-2; D017629:Gap Junctions / Q000378:metabolism*; D019044:Image Cytometry; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D018031:Connexin 43; D002118:Calcium; D016257:Fura-2