Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury

Abstract

The endoplasmic reticulum (ER) is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS). This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR), which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI) of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes.

Protective Role of Hepatocyte Cyclooxygenase‐2 Expression Against Liver Ischemia–Reperfusion Injury in Mice

“…Recent experimental data suggest the involvement of ERS in several liver diseases, including IRI . As a proof of concept, chemical chaperones such as 4‐phenylbutyrate are able to protect against IRI by inhibition of ERS .…”

Total Saponins of Aralia Elata (Miq) Seem Alleviate Calcium Homeostasis Imbalance and Endoplasmic Reticulum Stress-Related Apoptosis Induced by Myocardial Ischemia/Reperfusion Injury

“…ER also manages the release and uptake of Ca 2+ mainly through SERCA. Therefore, a close interaction between calcium homeostasis and ERS may exist [43]. When acute myocardial infarction generated myocardial hypoxemia, ATP was rapidly depleted and SERCA activity decreased.…”

“…In the early ERS, GRP78, the ERS marker, bound to unfolded proteins in ER and reduced the ER load, restoring homeostasis. If ERS was prolonged and aggravation, CHOP can initiate apoptotic signal pathway [6,43]. Our work aimed to study the intervention of AS on ERS by western blot.…”

Epigallocatechin Gallate Reduces Amyloid β‐Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress‐Mediated Apoptosis

“…Normally, Chaperone GRP78, a customary marker for ER stress, binds the N‐termini of three ER‐resident transmembrane proteins, such as IRE1, PERK, and ATF6, and inactivates them. However, in AD, excessive ER stress induces GRP78 away from them to activate the apoptosis‐associated ER stress signaling . CHOP, an ER‐stress apoptotic mediator, is upregulated by activation of PERK and ATF6, and triggers ER stress‐mediated apoptosis .…”