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Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation

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dc.citation.titleHeliyon
dc.citation.volume9
dc.creatorBlanco, Helga M.
dc.creatorPerez, Celia N.
dc.creatorBanchio, Claudia
dc.creatorAlvarez, Sergio E.
dc.creatorCiuffo, Gladys M.
dc.date.accessioned2024-05-24T15:14:08Z
dc.date.available2024-05-24T15:14:08Z
dc.date.issued2023
dc.description.abstractNeuroblastoma, the most common extracranial solid tumor occurring in childhood, originates from the aberrant proliferation of neural crest cells. Accordingly, the mechanism underling neuronal differentiation could provide new strategies for neuroblastoma treatment. It is well known that neurite outgrowth could be induced by Angiotensin II (Ang II) AT2 receptors; however, the signaling mechanism and its possible interaction with NGF (neural growth factor) receptors remain unclear. Here, we show that Ang II and CGP42112A (AT2 receptor agonist) promote neuronal differentiation by inducing neurite outgrowth and βIII-tubulin expression in SH-SY5Y neuroblastoma cells. In addition, we demonstrate that treatment with PD123319 (AT2 receptor antagonist) reverts Ang II or CGP42112A-induced differentiation. By using specific pharmacological inhibitors we established that neurite outgrowth induced by CGP42112A requires the activation of MEK (mitogen-activated protein kinase kinase), SphK (sphingosine ki- nase) and c-Src but not PI3K (phosphatidylinositol 3-kinase). Certainly, CGP42112A stimulated a rapid and transient (30 s, 1 min) phosphorylation of c-Src at residue Y416 (indicative of activation), following by a Src deactivation as indicated by phosphorylation of Y527. Moreover, inhibition of the NGF receptor tyrosine kinase A (TrkA) reduced neurite outgrowth induced by Ang IIand CGP42112A. In summary, we demonstrated that AT2 receptor-stimulated neurite outgrowth in SH-SY5Y cells involves the induction of MEK, SphK and c-Src and suggests a possible transactivation of TrkA. In that regard, AT2 signaling pathway is a key player in neuronal differentiation and might be a potential target for therapeutic treatments.
dc.description.filFil: Blanco, Helga M. Universidad Nacional de San Luis (UNSL). Facultad de Química, Bioquímica y Farmacia; Argentina.
dc.description.filFil: Perez, Celia N. Universidad Nacional de San Luis (UNSL). Facultad de Química, Bioquímica y Farmacia; Argentina.
dc.description.filFil: Perez, Celia N. Consejo Nacional de Investigaciones Científicas y Técnicas de San Luis. Instituto Multidisciplinario de Investigaciones (CONICET-IMIBIO-SL); Argentina.
dc.description.filFil: Banchio, Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Alvarez, Sergio E. Universidad Nacional de San Luis (UNSL). Facultad de Química, Bioquímica y Farmacia; Argentina.
dc.description.filFil: Alvarez, Sergio E. Consejo Nacional de Investigaciones Científicas y Técnicas de San Luis. Instituto Multidisciplinario de Investigaciones (CONICET-IMIBIO-SL); Argentina.
dc.description.filFil: Ciuffo, Gladys M. Universidad Nacional de San Luis (UNSL). Facultad de Química, Bioquímica y Farmacia; Argentina.
dc.description.filFil: Ciuffo, Gladys M. Consejo Nacional de Investigaciones Científicas y Técnicas de San Luis. Instituto Multidisciplinario de Investigaciones (CONICET-IMIBIO-SL); Argentina.
dc.description.sponsorshipUniversidad Nacional de San Luis: PROICO 02-0616
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas: PIP 656
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica: PICT 15-32350, PICT 2378-2014
dc.format.extent1-11
dc.identifier.issn2405-8440
dc.identifier.urihttps://hdl.handle.net/2133/27087
dc.language.isoen
dc.publisherElsevier
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2405844023028633?via%3Dihub
dc.relation.publisherversionhttps://doi.org/10.1016/j.heliyon.2023.e15656
dc.rightsopenAccess
dc.rights.holderBlanco, Helga M.
dc.rights.holderPerez, Celia N.
dc.rights.holderBanchio, Claudia
dc.rights.holderAlvarez, Sergio E.
dc.rights.holderCiuffo, Gladys M.
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAng II AT2 receptors
dc.subjectNeurite outgrowth
dc.subjectc-Src phosphorylation dephosphorylation
dc.subjectNeural growth factor
dc.titleNeurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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