Initial Glutathione Depletion During Short-Term Bed Rest: Pinpointing Synthesis and Degradation Checkpoints in the γ-Glutamyl Cycle DOI Creative Commons
Filippo Giorgio Di Girolamo, Filippo Mearelli,

Mariella Sturma

и другие.

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1430 - 1430

Опубликована: Ноя. 21, 2024

Hypokinesia triggers oxidative stress and accelerates the turnover of glutathione system via γ-glutamyl cycle. Our study aimed to identify regulatory checkpoints controlling intracellular levels. We measured intermediate substrates cycle in erythrocytes from 19 healthy young male volunteers before during a 10-day experimental bed rest. Additionally, we tracked changes levels specific metabolite ratios up 21 days Using gas chromatography-mass spectrometry internal standard technique, observed 9 ± 9% decrease first 5 rest, followed by an 11 increase 5th 10th day, nearly returning baseline ambulatory The cysteinyl-glycine-to-glutathione ratio, reflecting cyclotransferase activity (a key enzyme breakdown), rose 14 22% then fell 10 14% over subsequent days, again approaching cysteine-to-cysteine indicative cysteine synthetase (crucial for synthesis), increased 12 30% on day 29 41% results rest confirm those seen 10. By calculating ratio product concentration precursor concentration, assessed efficiency these enzymes turnover. These were corroborated directly measuring synthesis degradation rates vivo using stable isotope techniques. findings reveal significant kinetics initial potential therapeutic targets maintaining

Язык: Английский

Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder DOI Creative Commons
Ágnes Szabó, Zsolt Galla, Eleonóra Spekker

и другие.

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Язык: Английский

Процитировано

1
Modified Metabolic Syndrome Criteria Considering Cardio-Ankle Vascular Index (CAVI) and A Body Shape Index (ABSI): Implications for Kidney Risk DOI Creative Commons

Daiji Nagayama,

Yasuhiro Watanabe, Kohji Shirai

и другие.

Reviews in Cardiovascular Medicine, Год журнала: 2025, Номер 26(3)

Опубликована: Март 18, 2025

Waist circumference (WC), an abdominal obesity index in the current metabolic syndrome (MetS) criteria, may not adequately reflect visceral fat accumulation. This brief review aims to examine clinical significance of utilizing a body shape (ABSI), novel index, modify MetS considering predictive ability for vascular dysfunction indicated by cardio-ankle (CAVI), as well kidney function decline. First, relationship CAVI with is presented. Next, whether modification diagnostic criteria replacing high waist (WC-MetS) ABSI (ABSI-MetS) improves and discussed. Although limited Asian populations, several cross-sectional longitudinal studies support function. Increased associated decline, cutoff outcomes considered be 8-9. In urban residents who underwent health screening, increase ABSI, but mass (BMI) or WC, was increased CAVI, suggesting that reflects vasoinjurious composition. studies, ABSI-MetS superior WC-MetS identifying individuals CAVI. Furthermore, assessing decline enhanced only MetS, determined analysis. Using WC major criterion diagnosis identify at risk shows this problem solved ABSI. Future research should explore also predicts cardiovascular events, therapeutic intervention reduces outcomes.

Язык: Английский

Процитировано

0
Environmental Factors in the Etiology of Mental Disorders in the Czech Republic: Final Results DOI Creative Commons
Ladislav Hosák, Kristyna Hurdova, Jela Hrnčiarová

и другие.

Neuropsychiatric Disease and Treatment, Год журнала: 2025, Номер Volume 21, С. 541 - 545

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Targeting AMPK with Irisin: Implications for metabolic disorders, cardiovascular health, and inflammatory conditions — A systematic review DOI Creative Commons
Lucas Fornari Laurindo,

Victória Dogani Rodrigues,

Lívia Fornari Laurindo

и другие.

Life Sciences, Год журнала: 2024, Номер 360, С. 123230 - 123230

Опубликована: Ноя. 10, 2024

Irisin-based interventions have gained attention for their potential to modulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in various diseases. Physiologically, irisin is a myokine released during physical exercise that exerts anti-inflammatory effects and metabolic cardiometabolic enhancer. On other hand, AMPK crucial maintaining energy balance homeostasis. Therefore, individuals presenting low blood levels of dysregulation are more predisposed disorders cardiovascular health inflammatory conditions since regulating homeostasis preventing or treating these disorders. In light those mentioned above considering no review has addressed intricate relationships between regulation realm disorders, health, conditions, we comprehensively reviewed studies involving irisin's on signaling different models interventions. Our systematic analysis involved vitro studies, animal models, relevant clinical implications targeting due absence trials. The outcomes limitations included were extensively highlighted. Objectively, improved by enhancing β-cell function insulin secretion diabetes, mitigating myocardial injury reducing inflammation oxidative stress AMPK. However, lack trials limits generalizability findings human subjects. Future research should focus translating into applications exploring broader irisin-based health.

Язык: Английский

Процитировано

3
Initial Glutathione Depletion During Short-Term Bed Rest: Pinpointing Synthesis and Degradation Checkpoints in the γ-Glutamyl Cycle DOI Creative Commons
Filippo Giorgio Di Girolamo, Filippo Mearelli,

Mariella Sturma

и другие.

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1430 - 1430

Опубликована: Ноя. 21, 2024

Hypokinesia triggers oxidative stress and accelerates the turnover of glutathione system via γ-glutamyl cycle. Our study aimed to identify regulatory checkpoints controlling intracellular levels. We measured intermediate substrates cycle in erythrocytes from 19 healthy young male volunteers before during a 10-day experimental bed rest. Additionally, we tracked changes levels specific metabolite ratios up 21 days Using gas chromatography-mass spectrometry internal standard technique, observed 9 ± 9% decrease first 5 rest, followed by an 11 increase 5th 10th day, nearly returning baseline ambulatory The cysteinyl-glycine-to-glutathione ratio, reflecting cyclotransferase activity (a key enzyme breakdown), rose 14 22% then fell 10 14% over subsequent days, again approaching cysteine-to-cysteine indicative cysteine synthetase (crucial for synthesis), increased 12 30% on day 29 41% results rest confirm those seen 10. By calculating ratio product concentration precursor concentration, assessed efficiency these enzymes turnover. These were corroborated directly measuring synthesis degradation rates vivo using stable isotope techniques. findings reveal significant kinetics initial potential therapeutic targets maintaining

Язык: Английский

Процитировано

0