Adenosine 3',5'-cyclic monophosphate increases processing of amyloid precursor protein (APP) to beta-amyloid in neuroblastoma cells without changing APP levels or expression of APP mRNA.
Beta-Amyloid (Abeta), a 39-43 residue peptide generated by splicing of the amyloid precursor protein (APP), is one of the major components of senile plaques which are the hallmark of Alzheimer's disease (AD); and therefore, a role of Abeta in neuronal degeneration has been proposed. The factors which regulate the levels of Abeta have not been fully identified. Since an elevation of the intracellular levels of adenosine, 3', 5'-cyclic monophosphate (cAMP) in neuroblastoma cells (NB) induces terminal differentiation, and since these differentiated NB cells undergo spontaneous degeneration, the role of cAMP in the regulation of Abeta levels in these cells have been investigated. In order to determine the specificity of the effect of cAMP on nerve cells, rat glioma cells (C-6) were investigated in a similar manner. Results showed that an elevation of the levels of cAMP in NB cells enhances the intensity of Abeta immunostaining without changing the levels of APP or APP mRNA. This suggests that the rate of processing of APP to Abeta increases following an elevation of cAMP level in NB cells. Data also revealed that an elevation of cAMP level in glioma cells did not alter the intensity of staining with APP or Abeta.
Kumar
A
A
Center for Vitamins and Cancer Research, Department of Radiology, University of Colorado Health Sciences Center, Denver 80262, USA.
La Rosa
F G
FG
Hovland
A R
AR
Cole
W C
WC
Edwards-Prasad
J
J
Prasad
K N
KN
D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002338:Carotenoids / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D002338:Carotenoids; D000242:Cyclic AMP