Related Experiment Video
Updated: Jul 15, 2025
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
19.0K
Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review
Smriti Shreya1, Christophe F Grosset2, Buddhi Prakash Jain1
1Gene Expression and Signaling Lab, Department of Zoology, Mahatma Gandhi Central University, Motihari 845401, Bihar, India.
International Journal of Molecular Sciences
|September 28, 2023
Summary
Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR) to maintain cell function. UPR signaling is implicated in liver diseases, making UPR regulators potential therapeutic targets.
Area of Science:
- Cellular Biology
- Molecular Biology
- Hepatology
Background:
- The endoplasmic reticulum (ER) is crucial for protein synthesis and folding.
- ER dysfunction leads to unfolded protein accumulation and activates the unfolded protein response (UPR).
- The liver is a vital organ for detoxification and protein synthesis, susceptible to ER stress.
Purpose of the Study:
- To review the role of UPR signaling in various liver disorders.
- To explore UPR regulators as potential therapeutic targets for liver diseases.
Main Methods:
- Literature review of studies on ER stress and UPR in liver pathophysiology.
- Analysis of the mechanisms by which UPR branches (IRE1, PERK, ATF6) influence gene expression.
- Examination of the involvement of ER stress in hepatic diseases like fatty liver disease, cancer, hepatitis, and cholestasis.
Main Results:
- ER stress and UPR activation are common features in diverse hepatic disorders.
- UPR signaling pathways modulate cellular responses to stress, impacting liver function.
- Dysregulation of ER homeostasis contributes to the pathogenesis of liver diseases.
Conclusions:
- ER stress and UPR play significant roles in liver disease development and progression.
- Targeting UPR signaling pathways presents a promising therapeutic strategy for treating liver disorders.
- Further research is needed to fully elucidate the complex interplay between ER stress and liver disease.
Related Concept Videos
01:37The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
01:31Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
01:30Liver Physiology
609
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
609
01:24Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
01:29Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
02:26NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K