Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy
We aimed to characterize the mechanisms involved in neuroprotection by R-PIA administered before pilocarpine-induced seizures. Caspase-1 and caspase-3 activities were assayed using fluorimetry, and cathepsin D, HSP-70, and AKT expression levels were assayed using Western Blot of hippocampal samples....
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MDPI AG
2021-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/4/376 |
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| author | Daniele Suzete Persike Rebeca Padrão Amorim Puccinelli Maria José da Silva Fernandes |
| author_facet | Daniele Suzete Persike Rebeca Padrão Amorim Puccinelli Maria José da Silva Fernandes |
| author_sort | Daniele Suzete Persike |
| collection | DOAJ |
| description | We aimed to characterize the mechanisms involved in neuroprotection by R-PIA administered before pilocarpine-induced seizures. Caspase-1 and caspase-3 activities were assayed using fluorimetry, and cathepsin D, HSP-70, and AKT expression levels were assayed using Western Blot of hippocampal samples. R-PIA was injected before pilocarpine (PILO), and four groups were studied at 1 h 30 min and 7 days following initiation of status epilepticus (SE): PILO, R-PIA+PILO, SALINE, and R-PIA+SALINE. At 1 h 30 min, significantly higher activities of caspase-1 and -3 were observed in the PILO group than in the SALINE group. Caspase-1 and -3 activities were higher in the R-PIA+PILO group than in the PILO group. At 7 days following SE, caspase-1 and -3 activities were higher than in the initial post-seizure phase compared to the SALINE group. The pretreatment of rats receiving PILO significantly reduced caspase activities compared to the PILO group. Expression of HSP-70, AKT, and cathepsin D was significantly higher in the PILO group than in the SALINE. In the R-PIA+PILO group, the expression of AKT and HSP-70 was greater than in rats receiving only PILO, while cathepsin D presented decreased expression. Pretreatment with R-PIA in PILO-injected rats strongly inhibited caspase-1 and caspase-3 activities and cathepsin D expression. It also increased expression levels of the neuroprotective proteins HSP-70 and AKT, suggesting an important role in modulating the cellular survival cascade. |
| first_indexed | 2024-03-10T12:13:32Z |
| format | Article |
| id | doaj.art-85e75e607dc442188efad406731e22b5 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T12:13:32Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-85e75e607dc442188efad406731e22b52023-11-21T16:04:09ZengMDPI AGPharmaceuticals1424-82472021-04-0114437610.3390/ph14040376Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of EpilepsyDaniele Suzete Persike0Rebeca Padrão Amorim Puccinelli1Maria José da Silva Fernandes2Departamento de Neurologia/Neurocirurgia, Disciplina Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Rua Pedro de Toledo, 669, CEP, São Paulo 04039-032, BrazilDepartamento de Neurologia/Neurocirurgia, Disciplina Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Rua Pedro de Toledo, 669, CEP, São Paulo 04039-032, BrazilDepartamento de Neurologia/Neurocirurgia, Disciplina Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, Rua Pedro de Toledo, 669, CEP, São Paulo 04039-032, BrazilWe aimed to characterize the mechanisms involved in neuroprotection by R-PIA administered before pilocarpine-induced seizures. Caspase-1 and caspase-3 activities were assayed using fluorimetry, and cathepsin D, HSP-70, and AKT expression levels were assayed using Western Blot of hippocampal samples. R-PIA was injected before pilocarpine (PILO), and four groups were studied at 1 h 30 min and 7 days following initiation of status epilepticus (SE): PILO, R-PIA+PILO, SALINE, and R-PIA+SALINE. At 1 h 30 min, significantly higher activities of caspase-1 and -3 were observed in the PILO group than in the SALINE group. Caspase-1 and -3 activities were higher in the R-PIA+PILO group than in the PILO group. At 7 days following SE, caspase-1 and -3 activities were higher than in the initial post-seizure phase compared to the SALINE group. The pretreatment of rats receiving PILO significantly reduced caspase activities compared to the PILO group. Expression of HSP-70, AKT, and cathepsin D was significantly higher in the PILO group than in the SALINE. In the R-PIA+PILO group, the expression of AKT and HSP-70 was greater than in rats receiving only PILO, while cathepsin D presented decreased expression. Pretreatment with R-PIA in PILO-injected rats strongly inhibited caspase-1 and caspase-3 activities and cathepsin D expression. It also increased expression levels of the neuroprotective proteins HSP-70 and AKT, suggesting an important role in modulating the cellular survival cascade.https://www.mdpi.com/1424-8247/14/4/376epilepsypilocarpineadenosineA1-receptorneuroprotectioncaspases |
| spellingShingle | Daniele Suzete Persike Rebeca Padrão Amorim Puccinelli Maria José da Silva Fernandes Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy Pharmaceuticals epilepsy pilocarpine adenosine A1-receptor neuroprotection caspases |
| title | Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy |
| title_full | Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy |
| title_fullStr | Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy |
| title_full_unstemmed | Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy |
| title_short | Adenosine A1 Receptor Agonist (R-PIA) before Pilocarpine Modulates Pro- and Anti-Apoptotic Factors in an Animal Model of Epilepsy |
| title_sort | adenosine a1 receptor agonist r pia before pilocarpine modulates pro and anti apoptotic factors in an animal model of epilepsy |
| topic | epilepsy pilocarpine adenosine A1-receptor neuroprotection caspases |
| url | https://www.mdpi.com/1424-8247/14/4/376 |
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