Endoplasmic Reticulum Stress Signaling in the Regulation of Hepatic Pathological Responses

Abstract

The endoplasmic reticulum (ER) is a vital cell organelle that is primarily involved in the processes of protein folding, maintenance of intracellular calcium storage and lipid synthesis in order to maintain cellular homeostasis. To achieve this meticulous order, several ER-dependent processes have to be in unison and perfect harmony. However, a persistent supply of newly synthesized proteins strains the ER mainly due to the accumulation of unfolded proteins, thus ultimately leading to an imbalance termed ER stress. Although the accumulation of misfolded proteins is a frequent reason for the initiation of ER stress, it is also induced by the hyper-production of reactive oxygen species, aberrant calcium leakage from the ER and due to the effect of cytokines. ER stress signals are conveyed via three arms of ER, namely PERK, IRE1 and ATF6. Signal transduction form these signaling molecules often converges on the transcriptional upregulation of CHOP and its related signaling mechanisms. If the ER stress is unresolved, then it can lead to cell death through different cell death mechanisms, including apoptosis, proptosis, etc. In the liver, it has been observed that ER stress plays a critical role in hepatic damage under different experimental conditions. This review highlights the role of ER stress in liver pathologies.

Keywords

• ER stress
• liver disorders
• inflammasomes
• interleukin-1 cytokines