An update on lipotoxic endoplasmic reticulum stress in pancreatic β-cells

2008 ◽  
Vol 36 (5) ◽  
pp. 909-915 ◽  
Author(s):  
Miriam Cnop ◽  
Mariana Igoillo-Esteve ◽  
Daniel A. Cunha ◽  
Laurence Ladrière ◽  
Décio L. Eizirik
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Endoplasmic Reticulum Stress Response ◽  
Cell Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peripheral Tissues ◽  
Unfolded Protein

The UPR (unfolded protein response) or ER (endoplasmic reticulum) stress response was first described 20 years ago. The field of ER stress has expanded tremendously since, moving from basic biology in yeast to human neurodegenerative, inflammatory, cardiovascular and neoplastic diseases. The ER stress response has also been implicated in diabetes development, affecting both insulin production by pancreatic β-cells and insulin sensitivity in peripheral tissues. In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic β-cells. Recent advances in the understanding of lipotoxic ER stress and β-cell recovery from ER stress are discussed.

scholarly journals Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

2011 ◽  
Vol 10 (7) ◽  
pp. 895-901 ◽  
Author(s):  
Virginia E. Havel ◽  
Nathan K. Wool ◽  
David Ayad ◽  
Kurtis M. Downey ◽  
Christabel F. Wilson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Cryptococcus Neoformans ◽  
Deep Infection ◽  
Temperature Adaptation ◽  
Endoplasmic Reticulum Stress Response ◽  
Content Type ◽  
Unfolded Protein ◽  
Posttranscriptional Gene Regulation

ABSTRACT Adaptation to host temperature is a prerequisite for any pathogen capable of causing deep infection in humans. Our previous studies demonstrated that a Cryptococcus neoformans ccr4 Δ mutant lacking the major deadenylase involved in regulated mRNA decay was defective in host temperature adaptation and therefore virulence. In this study, the ccr4 Δ mutant was found to exhibit characteristics of chronic unfolded-protein response (UPR) engagement in both the gene expression profile and phenotype. We demonstrate that host temperature adaptation in C. neoformans is accompanied by transient induction of the endoplasmic reticulum (ER) stress response and that Ccr4-dependent posttranscriptional gene regulation contributes to resolution of ER stress during host temperature adaptation.

scholarly journals The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling

2021 ◽  
Author(s):  
Kashi Raj Bhattarai ◽  
Thoufiqul Alam Riaz ◽  
Hyung-Ryong Kim ◽  
Han-Jung Chae
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Stress Response ◽  
Er Stress ◽  
Protein Modification ◽  
Endoplasmic Reticulum Stress Response ◽  
Unfolded Protein ◽  
Er Stress Response ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractThe endoplasmic reticulum (ER) is an essential organelle of eukaryotic cells. Its main functions include protein synthesis, proper protein folding, protein modification, and the transportation of synthesized proteins. Any perturbations in ER function, such as increased demand for protein folding or the accumulation of unfolded or misfolded proteins in the ER lumen, lead to a stress response called the unfolded protein response (UPR). The primary aim of the UPR is to restore cellular homeostasis; however, it triggers apoptotic signaling during prolonged stress. The core mechanisms of the ER stress response, the failure to respond to cellular stress, and the final fate of the cell are not yet clear. Here, we discuss cellular fate during ER stress, cross talk between the ER and mitochondria and its significance, and conditions that can trigger ER stress response failure. We also describe how the redox environment affects the ER stress response, and vice versa, and the aftermath of the ER stress response, integrating a discussion on redox imbalance-induced ER stress response failure progressing to cell death and dynamic pathophysiological changes.

scholarly journals MANF: A Novel Endoplasmic Reticulum Stress Response Protein—The Role in Neurological and Metabolic Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yang Yu ◽  
Dan-yang Liu ◽  
Xue-shen Chen ◽  
Ling Zhu ◽  
Li-hong Wan
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Metabolic Disorders ◽  
Early Stage ◽  
Disease Diagnosis ◽  
Endoplasmic Reticulum Stress Response ◽  
Unfolded Protein ◽  
Potential Applications ◽  
Protein Response

The mesencephalic astrocyte-derived neurotrophic factor (MANF), also named as arginine-rich protein (ARP) or arginine-rich mutated in early-stage tumors (ARMET), is a novel evolutionary conserved protein related to unfolded protein response. Growing evidence suggests that MANF critically involves in many ER stress-related diseases with a protective effect. Here, we review the function of MANF based on its structure in neurological and metabolic disorders and summarize its potential applications in disease diagnosis and therapies.

scholarly journals Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1442
Author(s):  
Lena Krammes ◽  
Martin Hart ◽  
Stefanie Rheinheimer ◽  
Caroline Diener ◽  
Jennifer Menegatti ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Neurodegenerative Disorders ◽  
Endoplasmic Reticulum Stress Response ◽  
Caspase Activity ◽  
Therapeutic Approaches ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration.

scholarly journals Differential regulation of the endoplasmic reticulum stress response in pancreatic β-cells exposed to long-chain saturated and monounsaturated fatty acids

2008 ◽  
Vol 197 (3) ◽  
pp. 553-563 ◽  
Author(s):  
Eleftheria Diakogiannaki ◽  
Hannah J Welters ◽  
Noel G Morgan
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Initiation Factor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Er Stress Response ◽  
Stress Pathway ◽  
Long Chain

Exposure of pancreatic β-cells to long-chain fatty acids leads to the activation of some components of the endoplasmic reticulum (ER) stress pathway and this mechanism may underlie the ability of certain fatty acids to promote β-cell death. We have studied ER stress in BRIN-BD11 β-cells exposed to either the saturated fatty acid palmitate (C16:0) or the monounsaturated palmitoleate (C16:1). Palmitate (0.025–0.25 mM) induced the expression of various markers of the RNA-dependent protein kinase-like ER eukaryotic initiation factor 2α (eIF2α) kinase (PERK)-dependent pathway of ER stress (phospho-eIF2α; ATF4, activating transcription factor 4 and C/EBP homologous protein (CHOP-10)) although it failed to promote the expression of the ER chaperone GRP78. By contrast, palmitoleate did not induce any markers of the ER stress pathway even at concentrations as high as 1 mM. When palmitate and palmitoleate were added in combination, a marked attenuation of the ER stress response occurred. Under these conditions, the levels of phospho-eIF2α, ATF4 and CHOP-10 were reduced to less than those found in control cells. Palmitoleate also attenuated the ER stress response to the protein glycosylation inhibitor, tunicamycin, and improved the viability of the cells exposed to this agent. Exposure of the BRIN-BD11 cells to the protein phosphatase inhibitor, salubrinal, in the absence of fatty acids resulted in increased eIF2α phosphorylation but this was abolished by co-incubation with palmitoleate. We conclude that saturated fatty acids activate components of the PERK-dependent ER stress pathway in β-cells, ultimately leading to increased apoptosis. This effect is antagonised by monounsaturates that may exert their anti-apoptotic actions by regulating the activity of one or more kinase enzymes involved in mediating the phosphorylation of eIF2α.

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