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Activation of ER stress signalling increases mortality after a major trauma.
Abdullahi, Abdikarim; Barayan, Dalia; Vinaik, Roohi; Diao, Li; Yu, Nancy; Jeschke, Marc G.
Afiliação
  • Abdullahi A; Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Barayan D; Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
  • Vinaik R; Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Diao L; Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
  • Yu N; Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Jeschke MG; Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
J Cell Mol Med ; 24(17): 9764-9773, 2020 09.
Article em En | MEDLINE | ID: mdl-32810382
ABSTRACT
The endoplasmic reticulum (ER) adapts to stress by activating a signalling cascade known as the ER stress response. While ER stress signalling is a central component of the cellular defence against environmental insult, persistent activation is thought to contribute to the progression of various metabolic complications via loss of protein function and cell death. Despite its importance however, whether and how ER stress impacts morbidity and mortality in conditions of hypermetabolism remain unclear. In this study, we discovered that chronic ER stress response plays a role in mediating adverse outcomes that occur after major trauma. Using a murine model of thermal injury, we show that induction of ER stress with Tunicamycin not only increased mortality but also resulted in hepatic damage and hepatic steatosis. Importantly, post-burn treatment with chaperone ER stress inhibitors attenuated hepatic ER stress and improved organ function following injury. Our study identifies ER stress as a potential hub of the signalling network affecting multiple aspects of metabolism after major trauma and as a novel potential molecular target to improve the clinical outcomes of severely burned patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ferimentos e Lesões / Estresse do Retículo Endoplasmático / Fígado / Hepatopatias Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ferimentos e Lesões / Estresse do Retículo Endoplasmático / Fígado / Hepatopatias Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article