PKCζ-Mitogen-activated protein kinase signaling mediates crotalphine-Induced antinociception

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dc.contributor(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributorPrograma de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.authorFreitas, Bárbara Guimarães dept_BR
dc.contributor.authorHösch, Natália Gabrielept_BR
dc.contributor.authorPereira, Leandro Marciopt_BR
dc.contributor.authorBarbosa, Tereza Cristinapt_BR
dc.contributor.authorPicolo, Giselept_BR
dc.contributor.authorCury, Yarapt_BR
dc.contributor.authorZambelli, Vanessa Olzonpt_BR
dc.date.accessioned2022-01-10T21:04:28Z-
dc.date.available2022-01-10T21:04:28Z-
dc.date.issued2021pt_BR
dc.identifier.citationFreitas BG, Hösch NG, Pereira LM, Barbosa TC, Picolo G, Cury Y, et al. PKCζ-Mitogen-activated protein kinase signaling mediates crotalphine-Induced antinociception. Toxins. 2021 Dec; 13(12):912. doi:10.3390/toxins13120912.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/4083-
dc.description.abstractCrotalphine (CRP) is a structural analogue to a peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. This peptide induces a potent and long-lasting antinociceptive effect that is mediated by the activation of peripheral opioid receptors. The opioid receptor activation regulates a variety of intracellular signaling, including the mitogen-activated protein kinase (MAPK) pathway. Using primary cultures of sensory neurons, it was demonstrated that crotalphine increases the level of activated ERK1/2 and JNK-MAPKs and this increase is dependent on the activation of protein kinase Cζ (PKCζ). However, whether PKCζ-MAPK signaling is critical for crotalphine-induced antinociception is unknown. Here, we biochemically demonstrated that the systemic crotalphine activates ERK1/2 and JNK and decreases the phosphorylation of p38 in the lumbar spinal cord. The in vivo pharmacological inhibition of spinal ERK1/2 and JNK, but not of p38, blocks the antinociceptive effect of crotalphine. Of interest, the administration of a PKCζ pseudosubstrate (PKCζ inhibitor) prevents crotalphine-induced ERK activation in the spinal cord, followed by the abolishment of crotalphine-induced analgesia. Together, our results demonstrate that the PKCζ-ERK signaling pathway is involved in crotalphine-induced analgesia. Our study opens a perspective for the PKCζ-MAPK axis as a target for pain control.pt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(INCT-TOX) Instituto Nacional de Ciência e Tecnologia em Toxinaspt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.extent912pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofToxinspt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titlePKCζ-Mitogen-activated protein kinase signaling mediates crotalphine-Induced antinociceptionpt_BR
dc.title.alternativeA sinalização da proteína quinase ativada por PKCζ-mitógeno medeia a antinocicepção induzida por crotalfinapt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.3390/toxins13120912pt_BR
dc.identifier.urlhttps://doi.org/10.3390/toxins13120912pt_BR
dc.identifier.citationvolume13pt_BR
dc.identifier.citationissue12pt_BR
dc.subject.keywordanalgesic peptidept_BR
dc.subject.keywordprotein kinase Cpt_BR
dc.subject.keywordhyperalgesiapt_BR
dc.subject.keywordcell-signalingpt_BR
dc.relation.ispartofabbreviatedToxinspt_BR
dc.identifier.citationabntv. 13, n. 12, 912, dez. 2021pt_BR
dc.identifier.citationvancouver2021 Dec; 13(12):912pt_BR
dc.contributor.butantanFreitas, Bárbara Guimarães de|:Desvinculado|:(LEDS) Lab. Dor e Sinalização|:PrimeiroAutorpt_BR
dc.contributor.butantanHösch, Natália Gabriele|:Desvinculado|:(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributor.butantanPereira, Leandro Márcio|:Aluno Egresso|:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)|:(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributor.butantanBarbosa, Tereza Cristina|:Outros|:(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributor.butantanPicolo, Gisele|:Pesquisador|:Docente Permanente PPGTOX|:(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributor.butantanCury, Yara|:Pesquisador|:(LEDS) Lab. Dor e Sinalizaçãopt_BR
dc.contributor.butantanZambelli, Vanessa Olzon|:Pesquisador|:Docente Permanente PPGTOX|:(LEDS) Lab. Dor e Sinalização|:pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦305345/2011-7pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦444299/2014-9pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2011/04459-2pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2013/07467-1pt_BR
dc.sponsorship.butantanInstituto Nacional de Ciência e Tecnologia em Toxinas (INCT-TOX)¦¦573790/2008-6pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2008/57898-0pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦144228/2014-9pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦107340/2005-4pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦001pt_BR
dc.sponsorship.butantanFundaçao Butantan¦¦pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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