TY - JOUR
T1 - Endoplasmic reticulum stress in sepsis
AU - Khan, Mohammad Moshahid
AU - Yang, Weng Lang
AU - Wang, Ping
N1 - Publisher Copyright:
Copyright © 2015 by the Shock Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under stress and inflammatory conditions, ER loses homeostasis in its function, which is termed ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once stress is beyond the compensatory capacity of UPR or protracted, apoptosis would be initiated by triggering cell injuries, even cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidence that ER stress participates in the pathogenesis of sepsis. In this review, we summarize current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma-hemorrhage and ischemia/ reperfusion injury. We also discuss the potential implications of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis.
AB - Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under stress and inflammatory conditions, ER loses homeostasis in its function, which is termed ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once stress is beyond the compensatory capacity of UPR or protracted, apoptosis would be initiated by triggering cell injuries, even cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidence that ER stress participates in the pathogenesis of sepsis. In this review, we summarize current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma-hemorrhage and ischemia/ reperfusion injury. We also discuss the potential implications of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis.
KW - Apoptosis
KW - ER stress
KW - Inflammation
KW - Sepsis
KW - UPR
UR - http://www.scopus.com/inward/record.url?scp=84942083109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942083109&partnerID=8YFLogxK
U2 - 10.1097/SHK.0000000000000425
DO - 10.1097/SHK.0000000000000425
M3 - Review article
C2 - 26125088
AN - SCOPUS:84942083109
VL - 44
SP - 294
EP - 304
JO - Shock
JF - Shock
SN - 1073-2322
IS - 4
ER -