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Concentration-Dependent Effects of Protein Phosphatase (PP) Inhibitors Implicate PP1 and PP2A in Different Stages of Memory Formation
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bennett, Pauleen Zhao, Wei-qin Ng, Kim Tee |
| Copyright Year | 2001 |
| Abstract | Numerous studies have demonstrated roles for protein phosphorylation and for specific kinases in memory formation; however, a role for specific protein phosphatases has not been established. Previous studies using pharmacobehavioral methods to implicate protein phosphatase activity in memory formation have been unable to discriminate between protein phosphatases 1 (PP1) and 2A (PP2A), as available cell-permeable agents generally inhibit both enzyme classes. To address this difficulty the present study exploited differences in the potency of the selective phosphatase inhibitor, okadaic acid, toward PP1 and PP2A. Within the context of a temporally precise animal model of memory, developed using the day-old chick (Gallus domesticus), acute administration of various concentrations of okadaic acid was found to disrupt two temporally distinct stages of memory formation. When administered bilaterally into an area of the chick brain implicated in memory formation, concentrations of okadaic acid known to selectively inhibit PP2A in vitro disrupted memory from 50 min posttraining. Higher concentrations, reported to inhibit both PP2A and PP1 in vitro, produced significant retention deficits from 20 min posttraining. Identical temporally specific effects were also obtained by varying the concentration and time of administration of calyculin A, a phosphatase inhibitor with equal potency toward both enzyme classes. Hence, different phosphatase enzymes may contribute to different stages of the enzymatic cascade believed to underlie memory formation. |
| Starting Page | 91 |
| Ending Page | 110 |
| Page Count | 20 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S107474279993959X |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S107474279993959X?dgcid=api_sd_search-api-endpoint |
| PubMed reference number | 11124049v1 |
| Alternate Webpage(s) | https://doi.org/10.1006/nlme.1999.3959 |
| DOI | 10.1006/nlme.1999.3959 |
| Journal | Neurobiology of Learning and Memory |
| Volume Number | 75 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cascade Device Component Chickens Class Cognition Disorders In Vitro [Publication Type] Okadaic Acid Phosphoric Monoester Hydrolases Protein Phosphatase 2A Protein phosphorylation calyculin A phosphatase inhibitor phosphoric monoester hydrolase activity protein phosphatase activity |
| Content Type | Text |
| Resource Type | Article |