Search Results

You are looking at 1 - 5 of 5 items for

  • Author: Rui Curi x
Clear All Modify Search
Free access

Rosemari Otton, Danielly Oliveira da Silva, Thais Regina Campoio, Leonardo R Silveira, Maria Oliveira de Souza, Elaine Hatanaka and Rui Curi

Free access

Rosemari Otton, Danielly Oliveira da Silva, Thais Regina Campoio, Leonardo R Silveira, Maria Oliveira de Souza, Elaine Hatanaka and Rui Curi

Free access

Rosemari Otton, Danielly Oliveira da Silva, Thais Regina Campoio, Leonardo R Silveira, Maria Oliveira de Souza, Elaine Hatanaka and Rui Curi

Free access

Rosemari Otton, Danielly Oliveira da Silva, Thais Regina Campoio, Leonardo R Silveira, Maria Oliveira de Souza, Elaine Hatanaka and Rui Curi

Free access

José Edgar Nicoletti-Carvalho, Tatiane C Araújo Nogueira, Renata Gorjão, Carla Rodrigues Bromati, Tatiana S Yamanaka, Antonio Carlos Boschero, Licio Augusto Velloso, Rui Curi, Gabriel Forato Anhê and Silvana Bordin

Unfolded protein response (UPR)-mediated pancreatic β-cell death has been described as a common mechanism by which palmitate (PA) and pro-inflammatory cytokines contribute to the development of diabetes. There are evidences that interleukin 6 (IL6) has a protective action against β-cell death induced by pro-inflammatory cytokines; the effects of IL6 on PA-induced apoptosis have not been investigated yet. In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. In contrast to PA, IL6 efficiently reduced apoptosis induced by pro-inflammatory cytokines. In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2α kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. These findings suggest that IL6 is unable to protect pancreatic β-cells from PA-induced apoptosis because it does not repress UPR activation. In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT.