The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) Pathogenesis

American Journal Of Pathology, Journal Year: 2023, Volume and Issue: 193(12), P. 1887 - 1899

Published: Sept. 7, 2023

Perturbations in lipid and protein homeostasis induce endoplasmic reticulum (ER) stress metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty disease. Lipotoxic proteotoxic can activate the unfolded response (UPR) transducers: inositol requiring enzyme1α, PKR-like ER kinase, activating transcription factor 6α. Collectively, these pathways expression of genes that encode functions to resolve folding defect by increasing capacity degradation misfolded proteins. The is also intimately connected with metabolism, including de novo ceramide synthesis, phospholipid cholesterol droplet formation. Following their activation, UPR transducers regulate lipogenic liver. With persistent stress, cellular adaptation fails, resulting hepatocyte apoptosis, a pathological marker In addition ER–nucleus signaling activated UPR, interact other organelles via membrane contact sites. Modulating intracellular communication between endosomes, droplets, mitochondria restore could have therapeutic efficacy ameliorating Recent studies demonstrated cells convey release extracellular vesicles. This review discusses lipotoxic central role communicating MASLD pathogenesis. Metabolic disease, or MASLD, earlier most common chronic worldwide an overall prevalence 32.4%.1Riazi K. Azhari H. Charette J.H. Underwood F.E. King J.A. Afshar E.E. Swain M.G. Congly S.E. Kaplan G.G. 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Language: Английский

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The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126773 - 126773

Published: Sept. 9, 2023

Language: Английский

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TRIB3–TRIM8 complex drives NAFLD progression by regulating HNF4α stability

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(5), P. 778 - 791

Published: Jan. 21, 2024

Language: Английский

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Rabdosia rubescens (Hemsl.) H. Hara: A Potent Anti-Tumor Herbal Remedy - Botany, Phytochemistry, and Clinical Breakthroughs

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 340, P. 119200 - 119200

Published: Dec. 3, 2024

Language: Английский

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Homeostasis control in health and disease by the unfolded protein response

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Language: Английский

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Crosstalk between Endoplasmic Reticulum Stress and Ferroptosis in Liver Diseases

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(6), P. 221 - 221

Published: June 20, 2024

The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by accumulation misfolded proteins, elevated reactive oxygen species (ROS) levels, abnormal Ca2+ signaling, which was referred to stress (ERS). Ferroptosis a unique programmed cell death model mediated iron-dependent phospholipid peroxidation multiple signaling pathways. changes mitochondrial structure, damage glutathione peroxidase 4 (GPX4) excess iron were main characteristics ferroptosis. ROS produced ferroptosis can interfere with activity protein-folding enzymes, leading large amounts unfolded thus causing ERS. On contrary, increase ERS level promote ion lipid peroxide, up-regulation related genes. At present, studies on relationship between one-sided lack in-depth interaction mechanism. This review aimed explore molecular mechanism cross-talk ERS, provide new strategies targets for treatment liver diseases.

Language: Английский

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Inhibition of ER stress using tauroursodeoxycholic acid rescues obesity-evoked cardiac remodeling and contractile anomalies through regulation of ferroptosis

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 398, P. 111104 - 111104

Published: June 19, 2024

Language: Английский

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(+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 20, 2024

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles NAFLD pathogenesis. The unfolded protein response mitochondria (UPRmt) an adaptive mechanism that aims to restore mitochondrial homeostasis mitigate cellular stress. This study aimed investigate effects ( +)-Lipoic acid (ALA) on UPRmt, inflammation, oxidative vitro model using HepG2 cells treated with palmitic oleic induce steatosis. Results Treatment acids increased UPRmt-related proteins HSP90 HSP60 (heat shock protein), decreased CLPP (caseinolytic protease P), indicating ER activation. ALA treatment at 1 μM 5 restored levels. PA:OA (palmitic acid:oleic acid)-induced markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin BAX (Bcl-2-associated X protein) were significantly reduced treatment. also enhanced ER-mediated glycosylation stress, as evidenced GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi GSR (glutathione-disulfide reductase) expression GSH (Glutathione) levels, improved senescence shown β-galactosidase, γH2Ax Klotho-beta. Conclusions In conclusion, ameliorated inflammation acids, potentially offering therapeutic benefits for providing possible biochemical underlying beneficial effects. Graphical

Language: Английский

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Endoplasmic reticulum stress in liver fibrosis: Mechanisms and therapeutic potential

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167695 - 167695

Published: Jan. 1, 2025

Language: Английский

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Multifunctional integrated polyphenol-copper nanozymes for sepsis-induced acute liver injury via ameliorating endoplasmic reticulum stress and reprogramming inflammatory microenvironment

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160293 - 160293

Published: Feb. 1, 2025

Language: Английский

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