Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1314 - 1314

Published: Jan. 21, 2024

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from substrates oxygen produce adenosine triphosphate. also regulate proliferation, metastasis, and deterioration. The flow in mitochondrial respiratory chain generates reactive species (ROS), which harmful cells at high levels. stress caused by ROS accumulation has been associated with an increased risk cancer, cardiovascular liver diseases. Glutathione (GSH) is abundant cellular antioxidant that primarily synthesized cytoplasm delivered mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within A long-term imbalance ratio mGSH can cause dysfunction, apoptosis, necroptosis, ferroptosis, may lead disease. This study aimed review physiological functions, anabolism, variations organ tissue accumulation, delivery GSH mitochondria relationships between levels, GSH/GSH disulfide (GSSG) ratio, programmed death, ferroptosis. We discuss diseases deficiency related therapeutics.

Language: Английский

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Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 18, 2024

Introduction A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset acute disease. portion LC patients have symptoms similar to myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS), which results in a substantial reduction their quality life. better understanding pathophysiology LC, particular, ME/CFS is urgently needed. Methods We identified and studied metabolites soluble biomarkers plasma from mainly exhibiting compared age-sex-matched recovered (R) without COVID-19 (A), unexposed healthy (HC). Results Through these analyses, we alterations several metabolomic pathways vs other groups. Plasma metabolomics analysis showed differed R HC Of note, also exhibited different profile than HC. Moreover, observed significant elevation pro-inflammatory (e.g. IL-1α, IL-6, TNF-α, Flt-1, sCD14) but ATP patients. Our demonstrate exhibit persistent abnormalities 12 after such can be Hence, recovery period for with might long-lasting. In found sarcosine serine concentrations patients, was inversely correlated depression, anxiety, cognitive dysfunction scores. Conclusion study findings provide comprehensive knowledge base suggests supplementations potential therapeutic implications Finally, our reveals disproportionally affects females more males, evidenced by nearly 70% being female.

Language: Английский

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Glutathione Depletion and Stalwart Anticancer Activity of Metallotherapeutics Inducing Programmed Cell Death: Opening a New Window for Cancer Therapy

ACS Omega, Journal Year: 2024, Volume and Issue: 9(19), P. 20670 - 20701

Published: April 16, 2024

The cellular defense system against exogenous substances makes therapeutics inefficient as intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS) or nitrogen (RNS) other free radicals produced by the therapeutics. In cancer cell microenvironment, GSH level becomes exceptionally high to fight oxidative stress created production of ROS/RNS any radicals, which are byproducts redox reactions respiration processes. Thus, order maintain homeostasis for survival cells and their rapid proliferation, starts escalate. this circumstance, administration anticancer is vain, elevated reduces potential reduction they produce. Therefore, augment therapeutic agents condition, must be depleted hook crook. Hence, Review aims compile precisely role cells, importance its depletion therapy examples a few selected metal complexes able trigger death depleting level.

Language: Английский

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Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1098 - 1098

Published: Jan. 27, 2025

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web Science, PsycINFO, reference lists relevant up to 20 December 2024, highlighting central role Nrf2 pathway. As a critical regulator oxidative stress adaptation, mediates benefits these interventions. presents an innovative approach understanding regulation inflammation, its potential prevention treatment various diseases, including cancer, neurodegenerative disorders, cardiovascular pulmonary diabetes, inflammatory conditions, ageing, infections such as COVID-19. novelty this study is investigate bioactive compounds found (such polyphenols, flavonoids, vitamins) exercise-induced activation combined reveals their improve insulin sensitivity lipid metabolism reduce offering promising strategy for management chronic diseases. However, there are significant gaps current research, particularly regarding mechanisms interaction between diet, physical activity, activation, well long-term different populations, those with In addition, interactions other signalling pathways, AMPK, NF-κB, PI3K/Akt, collective contributions health explored. Furthermore, novel biomarkers presented assess impact strategies, NAD+/NADH ratio, GSH markers mitochondrial health. findings provide valuable insights into how integration antioxidant-rich diet regular can by activating related pathways represent strategies disorders. Further studies needed fully understand therapeutic interventions diseases stress, disease, cancer.

Language: Английский

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Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 834 - 834

Published: March 29, 2023

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It a ubiquitous molecule produced in organs, but its synthesis predominantly liver, tissue charge of storing and distributing it. GSH involved detoxification free radicals, peroxides xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, an important regulator cell homeostasis, since it participates signaling redox, regulation degradation proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, proliferation, DNA RNA synthesis, etc. transport vital step cellular homeostasis supported by liver through providing extrahepatic organs (such as kidney, lung, intestine, brain, among others) with said antioxidant. The wide range functions within which shows that glutathione’s role goes beyond being simple antioxidant agent; therefore, importance this tripeptide needs to be reassessed broader metabolic perspective.

Language: Английский

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Glutathione-responsive and -exhausting metal nanomedicines for robust synergistic cancer therapy

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: March 10, 2023

Due to their rapid and uncontrolled proliferation, cancer cells are characterized by overexpression of glutathione (GSH), which impairs reactive oxygen species (ROS)-based therapy weakens the chemotherapeutic agent-induced toxification. Extensive efforts have been made in past few years improve therapeutic outcomes depleting intracellular GSH. Special focus has given anticancer applications varieties metal nanomedicines with GSH responsiveness exhaustion capacity. In this review, we introduce several GSH-responsive -exhausting that can specifically ablate tumors based on high concentration cells. These include inorganic nanomaterials, metal-organic frameworks (MOFs), platinum-based nanomaterials. We then discuss detail extensively applied synergistic therapy, including chemotherapy, photodynamic (PDT), sonodynamic (SDT), chemodynamic (CDT), ferroptotic radiotherapy. Finally, present horizons challenges field for future development.

Language: Английский

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Glutathione: Lights and Shadows in Cancer Patients

Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2226 - 2226

Published: Aug. 8, 2023

In cases of cellular injury, there is an observed increase in the production reactive oxygen species (ROS). When this becomes excessive, it can result various conditions, including cancerogenesis. Glutathione (GSH), most abundant thiol-containing antioxidant, fundamental to re-establishing redox homeostasis. order evaluate role GSH and its antioxi-dant effects patients affected by cancer, we performed a thorough search on Medline EMBASE databases for relevant clinical and/or preclinical studies, with particular regard diet, toxicities, pharmacological processes. The conjugation xenobiotics, anti-cancer drugs, either two effects: xenobiotics may lose their harmful effects, or enhance toxicity inducing bioactivation. While being interesting weapon against chemotherapy-induced also have potential protective cancer cells. New studies are necessary better explain relationship between cancer. Although self-prescribed glutathione (GSH) implementation prevalent among intention reducing toxic anticancer treatments potentially preventing damage normal tissues, belief lacks substantial scientific evidence efficacy toxicity, except case cisplatin-related neurotoxicity. Therefore, use should only be considered under medical supervision, taking into account appropriate timing setting.

Language: Английский

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Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 1, 2024

Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy unclear mechanisms in several cell types, thymic epithelial cells (TECs). Here we report that the protein, C15ORF48, a critical inducer of autophagy. Mechanistically, C15ORF48 reduces membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase its downstream Unc-51-like 1. Interestingly, C15ORF48-dependent induction upregulates glutathione promoting survival reducing oxidative stress. Mice deficient C15orf48 show reduction TECs, but not typical starvation-induced skeletal muscles. Moreover,

Language: Английский

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Buffalo milk: an essential natural adjuvant

Discover Food, Journal Year: 2024, Volume and Issue: 4(1)

Published: June 13, 2024

Abstract The water buffalo breed known as the Murrah ( Bubalus bubalis ) is primarily raised for its milk. It preserved in Indian states of Haryana and Punjab, namely districts Bhiwani, Agra, Hisar, Rohtak, Jind, Jhajhar, Fatehabad, Gurgaon, Delhi capital city. fat from milk also contains ketoglycerides. While β-lactoglobulin, which branched chain essential amino acids well a retinol-binding protein that may modulate lymphatic processes, absent human milk, has somewhat more this than cow’s primary source whey protein. ability to create antimicrobial peptides work against gram-positive bacteria are released by proteolytic enzymes during trypsin-catalyzed digestion. International dairy product production increasingly shifting domestic substitute source. Buffalo high amount calcium, mineral necessary development bones. Moreover, it casein-derived peptides, promote bone health reduce likelihood osteoporosis, disorder characterized weakening bones an increased risk fractures. Customers love because excellent nutritional value. be eaten raw or used manufacture premium products like cheese, yogurt, ice cream, other traditional products.

Language: Английский

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Red emitting carbon dots for detection of endogenous glutathione with fluorescence enhancement and cell imaging

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2025, Volume and Issue: 333, P. 125901 - 125901

Published: Feb. 13, 2025

Language: Английский

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