| Title |
Downregulation of the cAMP/PKA Pathway in PC12 Cells Overexpressing NCS-1
|
|---|---|
| Published in |
Cellular and Molecular Neurobiology, September 2010
|
| DOI | 10.1007/s10571-010-9562-4 |
| Pubmed ID | |
| Authors |
Bruno R. Souza, Karen C. L. Torres, Débora M. Miranda, Bernardo S. Motta, Fernando S. Caetano, Daniela V. F. Rosa, Renan P. Souza, Antônio Giovani, Daniel S. Carneiro, Melissa M. Guimarães, Cristina Martins-Silva, Helton J. Reis, Marcus. V. Gomez, Andreas Jeromin, Marco A. Romano-Silva |
| Abstract |
It is well known that dopamine imbalances are associated with many psychiatric disorders and that the dopaminergic receptor D₂ is the main target of antipsychotics. Recently it was shown that levels of two proteins implicated in dopaminergic signaling, Neuronal calcium sensor-1 (NCS-1) and DARPP-32, are altered in the prefrontal cortex (PFC) of both schizophrenic and bipolar disorder patients. NCS-1, which inhibits D₂ internalization, is upregulated in the PFC of both patients. DARPP-32, which is a downstream effector of dopamine signaling, integrates the pathways of several neurotransmitters and is downregulated in the PFC of both patients. Here, we used PC12 cells stably overexpressing NCS-1 (PC12-NCS-1 cells) to address the function of this protein in DARPP-32 signaling pathway in vitro. PC12-NCS-1 cells displayed downregulation of the cAMP/PKA pathway, with decreased levels of cAMP and phosphorylation of CREB at Ser133. We also observed decreased levels of total and phosphorylated DARPP-32 at Thr34. However, these cells did not show alterations in the levels of D₂ and phosphorylation of DARPP-32 at Thr75. These results indicate that NCS-1 modulates PKA/cAMP signaling pathway. Identification of the cellular mechanisms linking NCS-1 and DARPP-32 may help in the understanding the signaling machinery with potential to be turned into targets for the treatment of schizophrenia and other debilitating psychiatric disorders. |
Mendeley readers
The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 3% |
| Unknown | 28 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 24% |
| Researcher | 7 | 24% |
| Professor | 4 | 14% |
| Student > Doctoral Student | 3 | 10% |
| Student > Bachelor | 3 | 10% |
| Other | 3 | 10% |
| Unknown | 2 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 13 | 45% |
| Neuroscience | 5 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 10% |
| Medicine and Dentistry | 3 | 10% |
| Immunology and Microbiology | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 3 | 10% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 August 2023.
All research outputs
#7,916,538
of 23,854,458 outputs
Outputs from Cellular and Molecular Neurobiology
#359
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Outputs of similar age
#35,759
of 98,193 outputs
Outputs of similar age from Cellular and Molecular Neurobiology
#1
of 3 outputs
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