Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

Biomolecules & Therapeutics, Journal Year: 2024, Volume and Issue: 32(3), P. 349 - 360

Published: April 11, 2024

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type iridoid glycoside contained

Language: Английский

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Enhancement of protein production in Aspergillus niger by engineering the antioxidant defense metabolism

Biotechnology for Biofuels and Bioproducts, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 29, 2024

Abstract Background Research on protein production holds significant importance in the advancement of food technology, agriculture, pharmaceuticals, and bioenergy. Aspergillus niger stands out as an ideal microbial cell factory for food-grade proteins, owing to its robust secretion capacity excellent safety profile. However, extensive oxidative folding proteins within endoplasmic reticulum (ER) triggers ER stress, consequently leading misfolding reactions. This stressful phenomenon results accelerated generation reactive oxygen species (ROS), thereby inducing stress. The accumulation ROS can adversely affect intracellular DNA, lipids. Result In this study, we enhanced detoxification A. (SH-1) by integrating multiple modules, including NADPH regeneration engineering module, glutaredoxin system, GSH synthesis transcription factor module. We assessed levels, growth under stress conditions, content. Our findings revealed that overexpression Glr1 system exhibited efficacy across various parameters. Specifically, it reduced levels 50%, boosted glucoamylase enzyme activity 243%, increased total 88%. Conclusion indicate moderate modulation redox conditions enhance overall output. conclusion, present a strategy augmenting propose potential approach optimizing system.

Language: Английский

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Paeoniflorin Induces ER Stress-Mediated Apoptotic Cell Death by Generating Nox4-Derived ROS under Radiation in Gastric Cancer

Nutrients, Journal Year: 2023, Volume and Issue: 15(24), P. 5092 - 5092

Published: Dec. 13, 2023

Gastric cancer is one of the most prevalent types worldwide, and its resistance to therapies, such as chemotherapy radiotherapy, has made treating it a major challenge. Paeoniflorin (PF) potential pharmacological treatment derived from paeony root. However, in cancer, molecular mechanisms biological functions PF are still unclear. In present study, we found that exerts anti-tumor effects vivo vitro induces apoptotic cell death through ER stress, calcium (Ca2+), reactive oxygen species (ROS) release gastric cells. ROS inhibition by DPI NAC blocks PERK signaling pathway via reduction Nox4. Moreover, triggers synergistic inhibitory effect epithelial-mesenchymal transition (EMT) process under radiation exposure radiation-resistant These findings indicate PF-induced Ca2+ overcomes radioresistance stress Therefore, PF, combination with radiation, may be powerful strategy for therapy.

Language: Английский

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Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4286 - 4308

Published: May 5, 2024

Coronaviruses represent a significant class of viruses that affect both animals and humans. Their replication cycle is strongly associated with the endoplasmic reticulum (ER), which, upon virus invasion, triggers ER stress responses. The activation unfolded protein response (UPR) within infected cells performed from three transmembrane receptors, IRE1, PERK, ATF6, results in reduction production, boost ER’s ability to fold proteins properly, initiation ER-associated degradation (ERAD) remove misfolded or proteins. However, cases prolonged severe stress, UPR can also instigate apoptotic cell death inflammation. Herein, we discuss ER-triggered host responses after coronavirus infection, as well pharmaceutical targeting potential antiviral strategy.

Language: Английский

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Pleiotropic Function of Cellular Prion Protein: Encompassing Endoplasmic‐Reticulum Stress, Cell Proliferation in Vascular Smooth Muscle Cells

Journal of Cellular Biochemistry, Journal Year: 2025, Volume and Issue: 126(1)

Published: Jan. 1, 2025

Cellular prion protein (PRNP) has been implicated in various physiological processes different cell types, for decades. Little known how PRNP functions multiple, yet related within a particular system. In our current study, with the aid of high-throughput RNA-sequencing technique, we have presented an overall transcriptome profile rat vascular smooth muscle cells (VSMCs) Prnp knockdown. Fifty-one genes were found to be differentially regulated, which, involved proliferation and endoplasmic reticulum (ER) stress pathway, show significant upregulation. That negatively regulates VSMC proliferation, demonstrated using immunoblot assays, BrdU incorporation assay Ki-67 immunofluorescence staining. As revealed from RNA-Seq data, ATF4, downstream effector PERK arm ER pathway is upregulated upon RNA interference VSMCs. result, expression functional phosphorylated isoform translation initiation factor eIF2α (p-eIF2α) elevated. Additionally, also showed that downregulation leads excess intracellular ROS accumulation, subsequently leading splicing Xbp1 mRNA triggering unfolded response (UPR) cell. Therefore, findings highlight directly or indirectly modulates array biological plays pivotal role preserving equilibrium between optimal function,

Language: Английский

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Multifaceted interplays between the essential players and lipid peroxidation in ferroptosis

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Bioengineered Versatile Heterojunctions as Stress Busters Targeting Matrix Degradation and Ferroptosis for Osteoarthritis Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage, with the underlying mechanism being inability chondrocytes to maintain homeostasis in response changing stress. The stress triggered excess ROS from various factors critical regulating chondrocyte survival and fate. In this study, 2D Mo 4/3 B 2‐ X MBene cerium‐gallic acid metal‐polyphenol network (MPN) together cartilage‐targeted shell hyaluronic WYRGRL (HW) are utilized development bio‐heterojunction MBene@MPN‐HW (MBM‐HW) through self‐assembly. MBM‐HW not only demonstrates superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme mimicking capabilities effectively scavenge ROS, but also exhibits dual‐responsive release cartilage‐targeting properties. Importantly, both vivo vitro experiments indicate that could alleviate oxidative stress, protect mitochondrial function, suppress cartilage matrix ferroptosis, thereby slowing progression OA. Mechanistically, it demonstrated attenuate Perk/eIF2α cascade mediated integrated restrain maintaining homeostasis. Overall, work underscores robust stress‐relieving capacity MBM‐HW, providing novel approach for treatment

Language: Английский

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PERK-Olating Through Cancer: A Brew of Cellular Decisions

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 248 - 248

Published: Feb. 8, 2025

The type I protein kinase PERK is an endoplasmic reticulum (ER) transmembrane that plays a multifaceted role in cancer development and progression, influencing tumor growth, metastasis, cellular stress responses. activation of represents one the three signaling pathways induced during unfolded response (UPR), which triggered, particular, cells constitutively experience various intracellular extracellular stresses impair folding within ER. can lead to both pro-survival proapoptotic outcomes, depending on context extent ER stress. It helps reprogramming gene expression cells, thereby ensuring survival face oncogenic stress, such as replicative DNA damage, also microenvironmental challenges, including hypoxia, angiogenesis, metastasis. Consequently, contributes initiation, transformation, adaptation microenvironment, chemoresistance. However, sustained cell proliferation promote apoptotic death by interconnected processes, mitochondrial dysfunction, translational inhibition, accumulation stresses, specific induction multifunctional factors, CHOP. dual promoting progression suppression makes it complex target for therapeutic interventions. A comprehensive understanding intricacies pathway their impact essential effective strategies, particularly diseases like cancer, where deregulated most, if not all, solid liquid tumors. This article provides overview knowledge acquired from study animal models lines cultured vitro PERK’s functions thus highlighting potential new avenues could this protein.

Language: Английский

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Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders

BioMetals, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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Mitigating doxorubicin-induced hepatotoxicity in male rats: The role of aerobic interval training and curcumin supplementation in reducing oxidative stress, endoplasmic reticulum stress and apoptosis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 24, 2025

Doxorubicin (DOXO) is a powerful anthracycline chemotherapeutic drug, but its clinical usage has been limited by deleterious effects on different organs, particularly hepatotoxicity. The aim of this study was to establish the combined aerobic interval training (AIT) and curcumin supplementation mitigating oxidative damage endoplasmic reticulum (ER) stress-mediated apoptosis in rat model DOXO-induced Fifty-six male Sprague–Dawley rats were randomly split into six groups: control (CON), vehicle, doxorubicin (Dox), + (Dox-C), AIT (Dox-A), (Dox-AC). DOXO intraperitoneally injected weekly (4 mg/kg/week) for five weeks. Curcumin (100 mg/kg/day) min at 80–90% VO2max intermitted 3 active rest 65–75% VO2max) conducted times week Finally, hepatic tissue blood samples collected assess histopathological changes, liver biomarkers, protein expression stress, ER markers. Tissue sections revealed that significantly improved hepatotoxicity induced DOXO, as evidenced positive alterations serum markers (P < 0.05). Both reduced DOXO-triggered damage, 0.05), with latter showing slightly higher effectiveness. Consequently, combination exhibits protective against chronic demonstrating relatively greater efficacy increasing antioxidant capacity reducing stress apoptosis.

Language: Английский

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