Abstract |
Previous studies reported disruption of adenylyl cyclase (AC)- cyclic AMP (cAMP) signal transduction in brain of Alzheimer's disease (AD). We also demonstrated that basal and stimulated AC activities in the presence of calcium and calmodulin (Ca(2+)/CaM) were significantly decreased in AD parietal cortex. In the present study, we examined the amounts of Ca(2+)/CaM-sensitive types I and VIII AC, and Ca(2+)/CaM-insensitive type VII AC in the postmortem hippocampi from AD patients and age-matched controls using immunoblotting. The specificities of the anti-type VII and VIII AC antibodies were confirmed by preabsorption with their specific blocking peptides. We observed a significant decrease in the level of type I AC and a tendency to decrease in the level of type VIII AC in AD hippocampus. On the other hand, the level of type VII AC showed no alteration between AD and controls. A body of evidence from the studies with invertebrates and vertebrates suggests that types I and VIII AC may play an essential role in learning and memory. Our finding thus firstly demonstrated that a specific disruption of the Ca(2+)/CaM-sensitive AC isoforms is likely involved in the pathophysiology in AD hippocampus.
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Authors | M Yamamoto, M E Götz, H Ozawa, C Luckhaus, T Saito, M Rösler, P Riederer |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1535
Issue 1
Pg. 60-8
(Dec 15 2000)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 11113632
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Calmodulin
- Isoenzymes
- Cyclic AMP
- Adenylyl Cyclases
- adenylyl cyclase 1
- adenylyl cyclase 8
- Calcium
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Topics |
- Adenylyl Cyclases
(analysis, immunology)
- Age Factors
- Aged
- Aged, 80 and over
- Alzheimer Disease
(enzymology, pathology)
- Antibodies
(immunology)
- Calcium
- Calmodulin
- Cyclic AMP
(metabolism)
- Down-Regulation
- Electrophoresis, Polyacrylamide Gel
- Female
- Hippocampus
(enzymology, pathology)
- Humans
- Immunoblotting
- Isoenzymes
(analysis)
- Male
- Middle Aged
- Neurons
(enzymology)
- Postmortem Changes
- Time Factors
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