The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1953 - 1953

Published: Nov. 1, 2023

Glutathione (GSH) is a ubiquitous tripeptide that biosynthesized in situ at high concentrations (1-5 mM) and involved the regulation of cellular homeostasis via multiple mechanisms. The main known action GSH its antioxidant capacity, which aids maintaining redox cycle cells. To this end, peroxidases contribute to scavenging various forms ROS RNS. A generally underestimated mechanism direct nucleophilic interaction with electrophilic compounds yielding thioether S-conjugates. Many compounds, including xenobiotics (such as NAPQI, simvastatin, cisplatin, barbital) intrinsic menadione, leukotrienes, prostaglandins, dopamine), form covalent adducts leading mainly their detoxification. In present article, we wish key role significance biology. This includes an update on formation GSH-S conjugates or emphasis given reaction, dependence GST (GSH S-transferase), where conjugation occurs tissues, significance. uncovering adducts' enhances our knowledge human metabolome. GSH-hematin were recently shown have been formed spontaneously multiples isomers hemolysates, structural destabilization endogenous toxin, hematin (free heme), derived from released hemoglobin. Moreover, hemin (the oxidized heme) has found act through Kelch-like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway epigenetic modulator metabolism. Last but not least, implications genetic defects metabolism, recorded hemolytic syndromes, cancer other pathologies, are presented discussed under framework conceptualizing S-conjugates could be regarded signatures metabolism diseased state.

Language: Английский

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Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 270, P. 116363 - 116363

Published: March 29, 2024

Language: Английский

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Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101058 - 101058

Published: Jan. 19, 2024

Language: Английский

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Glutathione and peroxisome redox homeostasis

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102917 - 102917

Published: Oct. 4, 2023

Despite intensive research on peroxisome biochemistry, the role of glutathione in peroxisomal redox homeostasis has remained a matter speculation for many years, and only recently this issue started to be experimentally addressed. Here, we summarize compare data from several organisms peroxisome-glutathione topic. It is clear comparison that repertoire glutathione-utilizing enzymes peroxisomes different varies widely. In addition, available suggest kinetic connectivity between cytosolic pools may also organisms, with some possessing membrane promptly permeable whereas others not case. However, regardless differences, picture emerges all these crucial component antioxidative system operates inside organisms.

Language: Английский

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The Role of Glutathione and Its Precursors in Type 2 Diabetes

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 184 - 184

Published: Feb. 1, 2024

Type 2 diabetes (T2D) is a major worldwide health crisis affecting about 6.2% of the world’s population. Alarmingly, one in five children USA have prediabetes. Glutathione (GSH) and its precursors play promising role prevention management type T2D. Oxidative stress (OxS) probable factor both T2D initiation progression. GSH cytosolic water-soluble chemical antioxidant emerging evidence supports improving outcomes. Dietary supplementation with N-acetyl-cysteine (NAC) and/or glycine (GLY), which are precursors, has also been studied for possible beneficial effects on This review will focus underlying pathophysiological molecular mechanisms linking OxS. In addition to their traditional roles, vivo GSH/NAC/GLY supplements be evaluated potential abilities modulate complex pro-oxidant factors (e.g., hyperglycemia) driving Positive feedback loops that amplify OxS over long time intervals likely result irreversible micro- macro-vascular damage. Most clinical studies focused adults or elderly. Future research pediatric populations should high priority since early intervention critical.

Language: Английский

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Ophthalmic acid is a glutathione regulating tripeptide

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(15), P. 3317 - 3330

Published: Jan. 20, 2024

Since its discovery in 1958 the lens of cows, ophthalmic acid (OPH) has stood shadow anti-oxidant analog: glutathione (GSH). Lacking thiol group that gives GSH many important properties, acid's function remained elusive, and it been widely presumed to be an accidental product same enzymes. In this review, we compile evidence demonstrating OPH is a ubiquitous metabolite found bacteria, plants, fungi, animals, produced through several layers metabolic regulation. We discuss limitations oft-repeated suggestions aberrations levels should solely indicate deficiency or oxidative stress. Finally, available literature suggest OPH's role metabolism as GSH-regulating tripeptide; controlling both cellular organelle influx efflux GSH, well modulating GSH-dependent reactions signaling. Ultimately, hope review reinvigorates directs more research into versatile metabolite.

Language: Английский

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Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116270 - 116270

Published: Feb. 15, 2024

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance iron homeostasis involves the process intake, storage output, dependening on iron-regulated protein/iron response element system operate tightly metabolism-related genes, including TFR1, DMT1, Fth, FPN. Dysregulation can lead overload, which increases virulence microbial colonisers occurrence oxidative stress, causing alveolar epithelial cells undergo necrosis apoptosis, form extracellular matrix. Accumulated drive iron-dependent ferroptosis exacerbated pulmonary fibrosis. Notably, chelator deferoxamine lipophilic antioxidant ferritin-1 have been shown attenuate inhibit lipid peroxidation in paper summarises regulatory mechanisms dysregulated metabolism development Targeting may be a potential therapeutic strategy for prevention treatment

Language: Английский

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Glutathione-Dependent Pathways in Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8423 - 8423

Published: Aug. 1, 2024

The most abundant tripeptide—glutathione (GSH)—and the major GSH-related enzymes—glutathione peroxidases (GPxs) and glutathione S-transferases (GSTs)—are highly significant in regulation of tumor cell viability, initiation development, its progression, drug resistance. high level GSH synthesis different cancer types depends not only on increasing expression key enzymes γ-glutamyl cycle but also changes transport velocity precursor amino acids. ability GPxs to reduce hydroperoxides is used for cellular each member GPx family has a mechanism action site maintaining redox balance. GSTs catalyze conjugation electrophilic substances reduction organic take part signaling pathways. By catalyzing S-glutathionylation target proteins, are involved processes, including metabolism (e.g., glycolysis PPP), signal transduction, transcription regulation, development resistance anticancer drugs. In this review, recent findings synthesis, roles functions GPxs, GST isoforms discussed, along with search inhibitors treatment.

Language: Английский

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Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5631 - 5631

Published: May 22, 2024

Chronic obstructive pulmonary disease (COPD), the major leading cause of mortality worldwide, is a progressive and irreversible respiratory condition characterized by peripheral airway lung parenchymal inflammation, accompanied fibrosis, emphysema, airflow limitation, has multiple etiologies, including genetic variance, air pollution, repetitive exposure to harmful substances. However, precise mechanisms underlying pathogenesis COPD have not been identified. Recent multiomics-based evidence suggests that plasticity alveolar macrophages contributes onset progression through coordinated modulation numerous transcription factors. Therefore, this review focuses on understanding functions macrophage polarization regulate homeostasis in COPD. These findings may provide better insight into distinct role perspective for developing novel therapeutic strategies targeting polarization.

Language: Английский

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Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(4), P. 463 - 463

Published: March 26, 2024

This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely tumor sites responding specific stimuli such as pH, temperature, light, hypoxia, redox conditions, thereby minimizing side effects associated with traditional chemotherapy. We discuss design, synthesis, recent applications polymersomes, emphasizing their ability improve therapeutic outcomes through controlled drug release delivery. Moreover, we highlight critical areas future research, including optimization polymersome–biological interactions biocompatibility, facilitate clinical adoption. Multi-responsive polymersomes emerge a promising development in nanomedicine, offering pathway safer effective treatments.

Language: Английский

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