title: ENDOPLASMIC RETICULUM STRESS IN SEPSIS.
abstract: 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.
authors.affiliation: *Center for Translational Research, The Feinstein Institute for Medical Research †Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York.
authors.forename: Mohammad Moshahid
authors.initials: MM
authors.lastname: Khan
authors.forename: Weng-Lang
authors.initials: WL
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D051702:Activating Transcription Factor 6 / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology; D018805:Sepsis / Q000503:physiopathology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology; D019892:eIF-2 Kinase / Q000502:physiology
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase