The unfolded protein response (UPR)--the endoplasmic reticulum stress response--is found in various pathologies including ischemia-reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods--a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems)--we identified the IRE1α-XBP1 and the ATF6 pathways as the main UPR effectors involved in cell's adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.febslet.2014.05.065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantitative Insights into Processivity of an Hsp100 Protein Disaggregase on Folded Proteins.
Biophys J
January 2025
Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:
The Hsp100 family of protein disaggregases play important roles in maintaining protein homeostasis in cells. E. coli ClpB is an Hsp100 protein that solubilizes protein aggregates.
View Article and Find Full Text PDFBetacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines.
Viruses
January 2025
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation.
View Article and Find Full Text PDFAlterations in Autophagic Function and Endoplasmic Reticulum Stress Markers in the Peripheral Blood Mononuclear Cells of Patients on Hemodialysis.
Int J Mol Sci
January 2025
Division of Renal Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung 433, Taiwan.
Oxidative stress, endoplasmic reticulum (ER) stress, and alterations in autophagy activity have been described as prominent factors mediating many pathological processes in chronic kidney disease (CKD). The accumulation of misfolded proteins in the ER may stimulate the unfolded protein response (UPR). The interplay between autophagy and UPR in hemodialysis (HD) patients remains unclear.
View Article and Find Full Text PDFKinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model.
Biomolecules
January 2025
Institute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Street, Novosibirsk 630090, Russia.
In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, N/N, O/O, and C/C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds N-H⋯O=C due to heavy isotope substitution decreases in the row H/D >> N/N > O/O > C/C.
View Article and Find Full Text PDFPharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma.
Biomolecules
January 2025
Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Ave., MSC509, Charleston, SC 29425, USA.
Cutaneous T-cell lymphoma (CTCL) is a rare T-cell malignancy characterized by inflamed and painful rash-like skin lesions that may affect large portions of the body's surface. Patients experience recurrent infections due to a compromised skin barrier and generalized immunodeficiency resulting from a dominant Th2 immune phenotype of CTCL cells. Given the role of the unfolded protein response (UPR) in normal and malignant T-cell development, we investigated the impact of UPR-inducing drugs on the viability, transcriptional networks, and Th2 phenotype of CTCL.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!