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Systemic effects of AGEs in ER stress induction in vivo.
Adamopoulos, Christos; Mihailidou, Chrysovalantou; Grivaki, Christofora; Papavassiliou, Kostas A; Kiaris, Hippokratis; Piperi, Christina; Papavassiliou, Athanasios G.
Afiliação
  • Adamopoulos C; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
  • Mihailidou C; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
  • Grivaki C; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
  • Papavassiliou KA; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
  • Kiaris H; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
  • Piperi C; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece. cpiperi@med.uoa.gr.
  • Papavassiliou AG; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
Glycoconj J ; 33(4): 537-44, 2016 08.
Article em En | MEDLINE | ID: mdl-27236787
Emerging evidence indicates that accumulation of advanced glycation end products (AGEs) in human tissues may contribute to cell injury, inflammation and apoptosis through induction of endoplasmic reticulum (ER) stress. Human metabolism relies on ER homeostasis for the coordinated response of all metabolic organs by controlling the synthesis and catabolism of various nutrients. In vitro studies have demonstrated AGE-induced enhancement of unfolded protein response (UPR) in different cell types including endothelial, neuronal, pancreatic cells and podocytes, suggesting this crosstalk as an underlying pathological mechanism that contributes to metabolic diseases. In this minireview, we describe in vivo studies undertaken by our group and others that demonstrate the diverse systemic effects of AGEs in ER stress induction in major metabolic tissues such as brain, kidney, liver and pancreas of normal mice. Administration of high-AGEs content diet to normal mice for the period of 4 weeks upergulates the mRNA and protein levels of ER chaperone Bip (GRP78) indicative of UPR initiation in all major metabolic organs and induces activation of the pivotal transcription factor XBP1 that regulates glucose and lipid metabolism. Furthermore, animals with genetic ablation of UPR-activated transcription factor C/EBP homologous protein CHOP allocated in high-AGEs diet, exhibited relative resistance to UPR induction (BiP levels) and XBP1 activation in major metabolic organs. Since CHOP presents a critical mediator that links accumulation and aggregation of unfolded proteins with induction of oxidative stress and ER stress-related apoptosis, it is revealed as an important molecular target for the management of metabolic diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Finais de Glicação Avançada / Apoptose / Metabolismo dos Lipídeos / Resposta a Proteínas não Dobradas / Estresse do Retículo Endoplasmático Limite: Animals / Humans Idioma: En Revista: Glycoconj J Assunto da revista: BIOQUIMICA / METABOLISMO Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Grécia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Finais de Glicação Avançada / Apoptose / Metabolismo dos Lipídeos / Resposta a Proteínas não Dobradas / Estresse do Retículo Endoplasmático Limite: Animals / Humans Idioma: En Revista: Glycoconj J Assunto da revista: BIOQUIMICA / METABOLISMO Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Grécia