c-Src kinase contributes on endothelial cells mechanotransduction in a heat shock protein 70-dependent turnover manner

Página do item simplificado
dc.contributor.authorPinto, Thaís Silva [UNESP]
dc.contributor.authorFernandes, Célio Junior da Costa [UNESP]
dc.contributor.authorda Silva, Rodrigo Augusto [UNESP]
dc.contributor.authorGomes, Anderson Moreira [UNESP]
dc.contributor.authorVieira, José Cavalcante Souza [UNESP]
dc.contributor.authorPadilha, Pedro de M. [UNESP]
dc.contributor.authorZambuzzi, Willian F. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2019-10-06T16:11:04Z
dc.date.available2019-10-06T16:11:04Z
dc.date.issued2019-07-01
dc.description.abstractShear stress changes are associated with a repertory of signaling cascade modulating vascular phenotype. As shear stress-related tensional forces might be associated with pathophysiological susceptibility, a more comprehensive molecular map needs to be addressed. Thus, we subjected human umbilical vein endothelial cells (HUVECs) to a circuit of different tensional forces in vitro considering the following three groups: (a) physiological blood flow shear stress condition (named Normo), (b) a hypertensive blood flow shear stress (named Hyper), and (c) these hyper-stressed cells were returned to Normo condition (named Return). The samples were properly collected to allow different methodologies analysis. Our data showed a pivotal involvement of c-Src on driving the mechanotransduction cascade by modulating signaling related with adhesion, survival (PI3K/Akt) and proliferative phenotype. Moreover, c-Src seems to develop important role during extracellular matrix remodeling. Additionally, proteomic analysis showed strong involvement of heat shock protein 70 (HSP70) in the hypertensive-stressed cells; it being significantly decreased in return phenotype. This result prompted us to investigate 20S proteasome as an intracellular proteolytic alternative route to promote the turnover of those proteins. Surprisingly, our data reveled significant overexpression of sets of proteasome subunit α-type (PSMA) and β-type (PSMB) genes. In conjunction, our data showed c-Src as a pivotal protein to drive mechanotransduction in endothelial cells in a HSP70-dependent turnover scenario. Because shear patterns is associated with pathophysiological changes, such as atherosclerosis and hypertension, these results paved new road to understand the molecular mechanism on driving mechanotransduction in endothelial cells and, if drugable, these targets must be considered within pharmacological treatment optimization.en
dc.description.affiliationDepartment of Chemistry and Biochemistry São Paulo State University (UNESP) Institute of Biosciences
dc.description.affiliationElectron Microscopy Center São Paulo State University (UNESP) Institute of Biosciences
dc.description.affiliationUnespDepartment of Chemistry and Biochemistry São Paulo State University (UNESP) Institute of Biosciences
dc.description.affiliationUnespElectron Microscopy Center São Paulo State University (UNESP) Institute of Biosciences
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2014/22689-3
dc.description.sponsorshipIdFAPESP: 2017/18349-0
dc.format.extent11287-11303
dc.identifierhttp://dx.doi.org/10.1002/jcp.27787
dc.identifier.citationJournal of Cellular Physiology, v. 234, n. 7, p. 11287-11303, 2019.
dc.identifier.doi10.1002/jcp.27787
dc.identifier.issn1097-4652
dc.identifier.issn0021-9541
dc.identifier.scopus2-s2.0-85058843086
dc.identifier.urihttp://hdl.handle.net/11449/188528
dc.language.isoeng
dc.relation.ispartofJournal of Cellular Physiology
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectc-Src
dc.subjectendothelial cells
dc.subjectHSP70
dc.subjecthypertension
dc.subjectmechanotransduction
dc.subjectproteasome
dc.subjectshear stress
dc.subjectsignaling
dc.titlec-Src kinase contributes on endothelial cells mechanotransduction in a heat shock protein 70-dependent turnover manneren
dc.typeArtigo
unesp.author.orcid0000-0002-4149-5965[7]

Arquivos

Coleções

Botucatu - CME - Centro de Microscopia Eletrônica