Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons

Detalhes bibliográficos
Autor(a) principal: Silva, Carla G.
Data de Publicação: 2007
Outros Autores: Porciúncula, Lisiane O., Canas, Paula M., Oliveira, Catarina R., Cunha, Rodrigo A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/4713
https://doi.org/10.1016/j.nbd.2007.04.018
Resumo: Since adenosine A2A receptor (A2ARs) blockade protects against noxious brain insults involving apoptosis, we directly tested if A2AR blockade prevents apoptosis induced by staurosporine (STS). Exposure of rat hippocampal neurons to STS (30 nM, 24 h) decreased neuronal viability while increasing the number apoptotic-like neurons and de-localizing mitochondria and cytochrome c immunoreactivities. This was prevented by the selective A2AR antagonists, SCH58261 and ZM241385 (50 nM). Shorter incubation periods (6 h) with STS caused no neuronal loss but decreased synaptophysin and MAP-2 immunoreactivities, which was prevented by SCH58261. Furthermore, STS (100 nM) decreased MTT reduction and increased caspase-3 activity in rat hippocampal nerve terminals, which was prevented by SCH58261. These results show that A2AR blockade inhibits STS-induced apoptotic-like neuronal cell death. This begins with an apoptotic-like synaptotoxicity, which later evolved into an overt neurotoxicity, and A2ARs effectively control this initial synaptotoxicity, in agreement with their predominant synaptic localization in the hippocampus.
id RCAP_f38af00060ad17c4944fd66692fa089f
oai_identifier_str oai:estudogeral.uc.pt:10316/4713
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neuronsAdenosineA2A receptorStaurosporineApoptosisNeuroprotectionMitochondriaHippocampusCultured neuronsSynaptosomesCaspase-3Since adenosine A2A receptor (A2ARs) blockade protects against noxious brain insults involving apoptosis, we directly tested if A2AR blockade prevents apoptosis induced by staurosporine (STS). Exposure of rat hippocampal neurons to STS (30 nM, 24 h) decreased neuronal viability while increasing the number apoptotic-like neurons and de-localizing mitochondria and cytochrome c immunoreactivities. This was prevented by the selective A2AR antagonists, SCH58261 and ZM241385 (50 nM). Shorter incubation periods (6 h) with STS caused no neuronal loss but decreased synaptophysin and MAP-2 immunoreactivities, which was prevented by SCH58261. Furthermore, STS (100 nM) decreased MTT reduction and increased caspase-3 activity in rat hippocampal nerve terminals, which was prevented by SCH58261. These results show that A2AR blockade inhibits STS-induced apoptotic-like neuronal cell death. This begins with an apoptotic-like synaptotoxicity, which later evolved into an overt neurotoxicity, and A2ARs effectively control this initial synaptotoxicity, in agreement with their predominant synaptic localization in the hippocampus.http://www.sciencedirect.com/science/article/B6WNK-4NTRT29-1/1/e8601014d0729171e70d9df284a404422007info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/4713http://hdl.handle.net/10316/4713https://doi.org/10.1016/j.nbd.2007.04.018engNeurobiology of Disease. 27:2 (2007) 182-189Silva, Carla G.Porciúncula, Lisiane O.Canas, Paula M.Oliveira, Catarina R.Cunha, Rodrigo A.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-11-06T16:49:17Zoai:estudogeral.uc.pt:10316/4713Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:43:26.665990Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
title Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
spellingShingle Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
Silva, Carla G.
Adenosine
A2A receptor
Staurosporine
Apoptosis
Neuroprotection
Mitochondria
Hippocampus
Cultured neurons
Synaptosomes
Caspase-3
title_short Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
title_full Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
title_fullStr Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
title_full_unstemmed Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
title_sort Blockade of adenosine A2A receptors prevents staurosporine-induced apoptosis of rat hippocampal neurons
author Silva, Carla G.
author_facet Silva, Carla G.
Porciúncula, Lisiane O.
Canas, Paula M.
Oliveira, Catarina R.
Cunha, Rodrigo A.
author_role author
author2 Porciúncula, Lisiane O.
Canas, Paula M.
Oliveira, Catarina R.
Cunha, Rodrigo A.
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Silva, Carla G.
Porciúncula, Lisiane O.
Canas, Paula M.
Oliveira, Catarina R.
Cunha, Rodrigo A.
dc.subject.por.fl_str_mv Adenosine
A2A receptor
Staurosporine
Apoptosis
Neuroprotection
Mitochondria
Hippocampus
Cultured neurons
Synaptosomes
Caspase-3
topic Adenosine
A2A receptor
Staurosporine
Apoptosis
Neuroprotection
Mitochondria
Hippocampus
Cultured neurons
Synaptosomes
Caspase-3
description Since adenosine A2A receptor (A2ARs) blockade protects against noxious brain insults involving apoptosis, we directly tested if A2AR blockade prevents apoptosis induced by staurosporine (STS). Exposure of rat hippocampal neurons to STS (30 nM, 24 h) decreased neuronal viability while increasing the number apoptotic-like neurons and de-localizing mitochondria and cytochrome c immunoreactivities. This was prevented by the selective A2AR antagonists, SCH58261 and ZM241385 (50 nM). Shorter incubation periods (6 h) with STS caused no neuronal loss but decreased synaptophysin and MAP-2 immunoreactivities, which was prevented by SCH58261. Furthermore, STS (100 nM) decreased MTT reduction and increased caspase-3 activity in rat hippocampal nerve terminals, which was prevented by SCH58261. These results show that A2AR blockade inhibits STS-induced apoptotic-like neuronal cell death. This begins with an apoptotic-like synaptotoxicity, which later evolved into an overt neurotoxicity, and A2ARs effectively control this initial synaptotoxicity, in agreement with their predominant synaptic localization in the hippocampus.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/4713
http://hdl.handle.net/10316/4713
https://doi.org/10.1016/j.nbd.2007.04.018
url http://hdl.handle.net/10316/4713
https://doi.org/10.1016/j.nbd.2007.04.018
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Neurobiology of Disease. 27:2 (2007) 182-189
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv aplication/PDF
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799133706605035520