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AKT activation seems to be associated with apoptotic signals and not with pro-survival signals in a pristane-induced lupus model.
|Authors:||García-Rodríguez, Sonia ; Rosal-Vela, Antonio; Botta, Davide; Cumba García, Luz M.; Zumaquero, Esther; Prados-Maniviesa, Verónica; Cerezo-Wallis, Daniela; Lo Buono, Nicola; Robles-Guirado, José-Ángel; Guerrero, Salvador; González-Paredes, Elena; Andrés-León, Eduardo CSIC ORCID ; Corbí, Angel L. CSIC ORCID; Mack, Matthias; Koch-Nolte, Friedrich; Merino, Ramón CSIC ORCID; Zubiaur, Mercedes CSIC ORCID ; Lund, Frances E.; Sancho, Jaime CSIC ORCID||Issue Date:||15-Oct-2018||Abstract:||Several studies have shown that in addition to its role as a survival factor and tumor promoting agent, AKT is also able to exhibit pro-apoptotic effects under diverse conditions, including oxidative stress, cytokine stimulation and exposure to cytotoxic chemicals like staurosporine, methotrexate, docetaxel and etoposide. Moreover, phosphorylation of second mitochondria-derived activator of caspases (SMAC) by AKT promotes caspase-3 activation during etoposide-induced apoptosis in HeLa cells. Our data show that injection of pristane into the peritoneum induces apoptosis-mediated cell death of peritoneal exudate cells (PECs), as evidenced by the increased number of annexin V+ peritoneal cells and their increased levels of cleaved/active caspase-3. Indeed, the higher levels of activated caspase-3 protein in WT PECs, particularly at 2-weeks post pristane treatment, are indicative of a higher rate of apoptosis compared to Cd38¿/¿ cells. In contrast, no differences were observed in the levels of MCL-1, an anti-apoptotic protein and member of the BCL2 family. Furthermore, kinases ERK1/2 and AKT showed distinct activation kinetics in pristane-elicited PECs. Interestingly, caspase-3 activation followed similar kinetics to AKT activation in both WT and Cd38¿/¿ PECs, while ERK activation correlated with increased levels of MCL-1. In summary our data strongly suggest that in the pristane-induced lupus model AKT activation is associated with apoptotic signals and not with survival signals. Further studies, however, are required to identify specific pro- and anti-apoptotic target proteins that are phosphorylated by ERK or AKT following pristane treatment, and that regulate the apoptotic process.||URI:||http://hdl.handle.net/10261/229175|
|Appears in Collections:||(IPBLN) Comunicaciones congresos|
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