Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation
Neuroblastoma, 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 outg...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | Argentina |
| Institution: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repository: | CONICET Digital (CONICET) |
| Language: | English |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/227341 |
| Online Access: | http://hdl.handle.net/11336/227341 |
| Access Level: | Open access |
| Keyword: | ANG II AT2 RECEPTORS C-SRC PHOSPHORYLATION/ DEPHOSPHORYLATION NEURAL GROWTH FACTOR NEURITE OUTGROWTH https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| _version_ | 1878403563543068672 |
|---|---|
| author | Blanco, Helga Myrna |
| author2 | Perez, Celia Noemí Banchio, Claudia Elena Alvarez, Sergio Eduardo Ciuffo, Gladys Maria |
| author2_role | author author author author |
| author_browse | Alvarez, Sergio Eduardo Banchio, Claudia Elena Blanco, Helga Myrna Ciuffo, Gladys Maria Perez, Celia Noemí |
| author_facet | Blanco, Helga Myrna Perez, Celia Noemí Banchio, Claudia Elena Alvarez, Sergio Eduardo Ciuffo, Gladys Maria |
| author_role | author |
| collection | CONICET Digital (CONICET) |
| description | Neuroblastoma, 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 kinase) 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 II and 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | AR_95eefe8ef3b5800a3962c8fc45c8f89d |
| identifier_str_mv | Blanco, Helga Myrna; Perez, Celia Noemí; Banchio, Claudia Elena; Alvarez, Sergio Eduardo; Ciuffo, Gladys Maria; Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation; Elsevier; Heliyon; 9; 5; 4-2023; 1-11 2405-8440 CONICET Digital CONICET |
| institution | Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str | Consejo Nacional de Investigaciones Científicas y Técnicas |
| language | eng |
| network_acronym_str | AR |
| network_name_str | Argentina |
| oai_identifier_str | oai:ri.conicet.gov.ar:11336/227341 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | CONICET Digital (CONICET) |
| spelling | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation Blanco, Helga Myrna Perez, Celia Noemí Banchio, Claudia Elena Alvarez, Sergio Eduardo Ciuffo, Gladys Maria ANG II AT2 RECEPTORS C-SRC PHOSPHORYLATION/ DEPHOSPHORYLATION NEURAL GROWTH FACTOR NEURITE OUTGROWTH https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 Neuroblastoma, 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 kinase) 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 II and 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. Fil: Blanco, Helga Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Perez, Celia Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Banchio, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Elsevier http://hdl.handle.net/11336/227341 Blanco, Helga Myrna; Perez, Celia Noemí; Banchio, Claudia Elena; Alvarez, Sergio Eduardo; Ciuffo, Gladys Maria; Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation; Elsevier; Heliyon; 9; 5; 4-2023; 1-11 2405-8440 CONICET Digital CONICET |
| spellingShingle | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation Blanco, Helga Myrna ANG II AT2 RECEPTORS C-SRC PHOSPHORYLATION/ DEPHOSPHORYLATION NEURAL GROWTH FACTOR NEURITE OUTGROWTH https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| status_str | publishedVersion |
| title | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| title_full | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| title_fullStr | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| title_full_unstemmed | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| title_short | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| title_sort | Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation |
| topic | ANG II AT2 RECEPTORS C-SRC PHOSPHORYLATION/ DEPHOSPHORYLATION NEURAL GROWTH FACTOR NEURITE OUTGROWTH https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| topic_facet | ANG II AT2 RECEPTORS C-SRC PHOSPHORYLATION/ DEPHOSPHORYLATION NEURAL GROWTH FACTOR NEURITE OUTGROWTH https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| url | http://hdl.handle.net/11336/227341 |