Physiological levels of beta-amyloid peptide promote PC12 cell proliferation.
Alzheimer's beta-amyloid peptide (A beta) is normally present at a subnanomolar (225-625 pM) concentration in body fluids and in the medium of cultured cells. The potential actions of physiologic levels of A beta are being investigated. We have recently shown that nanomolar doses of A beta can stimulate tyrosine phosphorylation and activate phosphatidylinositol-3-kinase in neuronal cells. Here we show evidence that A beta at nanomolar levels promotes cell growth determined by [3H]thymidine incorporation, protein content and cell counts. Physiological levels of A beta peptides, including 1-40, 1-42, 25-35, all promote growth of PC12 cells in low serum medium with doubling times of 71 h to around 30 h. Although the promotion of cell proliferation can be detected at nanomolar levels of A beta, it's potency is less than that of serum. This suggests that A beta may normally play a neurotrophic/mitogenic role in neuronal biology.
Molecular Physiology and Genetics Section, NIA, Baltimore, MD 21224, USA.
Y
Y
Luo
T
T
Sunderland
G S
GS
Roth
B
B
Wolozin
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016716:PC12 Cells; D051381:Rats; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008934:Mitogens; D009419:Nerve Tissue Proteins; D013936:Thymidine