Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

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The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit

Frontiers in Integrative Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: March 29, 2022

Overweight and obesity are now considered a worldwide pandemic growing public health problem with severe economic social consequences. Adipose tissue is an organ neuroimmune-endocrine functions, which participates in homeostasis. So, adipocyte hypertrophy hyperplasia induce state of chronic inflammation that causes changes the brain neuroinflammation. Studies obese animal models patients have shown relationship between diet cognitive decline, especially working memory learning deficiencies. Here we analyze how obesity-related peripheral can affect central nervous system physiology, generating Given blood-brain barrier interface periphery system, its altered physiology may mediate consequences on various processes. Finally, several interventions, use natural compounds exercise to prevent adverse effects also discussed.

Language: Английский

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Nitrotyrosine, Nitrated Lipoproteins, and Cardiovascular Dysfunction in Patients with Type 2 Diabetes: What Do We Know and What Remains to Be Explained?

Antioxidants, Journal Year: 2022, Volume and Issue: 11(5), P. 856 - 856

Published: April 27, 2022

Diabetes mellitus (DM) is a strong risk factor for the development of cardiovascular diseases (CVDs), which are most important cause morbidity and mortality in population patients living with DM. DM associated lipid metabolism disorders characterized by decrease high-density lipoprotein blood concentration, an increase triglyceride presence modified lipoproteins not routinely measured clinical practice. Nitrated produced nitration tyrosyl residues apolipoproteins myeloperoxidase. There some evidence from research conducted showing that nitrated may play role dysfunction, but this issue requires further investigation. It was found HDL particles caspase-3 paraoxonase-1 activity, as well activity cholesterol transport via ABCA1, reduces protective effect on system. Less information has been collected about LDL particles. Thus far, much more obtained relationship nitrotyrosine expression factors dysfunction. The purpose paper to provide extensive review literature present current state knowledge association between dysfunction system, especially Moreover, directions future area were discussed.

Language: Английский

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Advanced oxidation protein products induce apoptosis in thyroid follicular epithelial cells through oxidative stress in Hashimoto’s thyroiditis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114069 - 114069

Published: Jan. 18, 2025

Language: Английский

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De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 9, 2022

Glycine is a dietary non-essential amino acid that low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear it unknown whether hypoglycinemia cause or consequence of insulin resistance.Using multiple isotopically labeled tracers, we aimed to determine underlying kinetic changes for by: 1) Comparing glycine kinetics between participants with morbid (BMI ≥ 32.5 kg/m2) those healthy weight < 25 kg/m2), 2) after surgery.[1,2-13C2] glycine, [2,3,3-2H3] serine, [2H5] phenylalanine were infused compare parameters 21 controls weight. Participants then underwent surgery 17 re-studied 6 months later. Data analyzed by non-parametric methods presented as median (interquartile range).Compared controls, had significantly lower plasma concentrations at 163 (153-171) vs. 201 (172-227) µmol/L reduced de novo synthesis rate 86.2 (64.5-111) vs.124 (103-159) µmol·kg LBM-1·h1, p 0.001. Following surgery, body resistance decreased this was accompanied significant concentration 210 (191-243) well 127 (98.3-133) LBM-1·h-1, 0.001 baseline.Hypoglycinemia associated impaired synthesis. The increase plus marked improvement suggest may be secondary because obesity-induced resistance.[https://tinyurl.com/6wfj7yss], identifier [NCT04660513].

Language: Английский

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A new aspect of metabolic disorders in obesity: carbonyl stress

Сибирский научный медицинский журнал, Journal Year: 2024, Volume and Issue: 43(6), P. 24 - 33

Published: Jan. 10, 2024

The literature review examines the problem of obesity in modern society. It has been shown that aggravates concomitant diseases, increases probability developing metabolic disorders and related pathologies, risk complications mortality. secretory function adipose tissue, its participation regulation biological processes is considered detail. concept carbonyl stress components revealed, role compounds body described, pathways leading to formation reaction products are shown, free radicals these noted. mechanisms pathogenesis associated with development discussed; greatest contribution car bonyl pathology made by two types processes: lipid peroxidation reactions resulting lipoperoxidation activated hyperglycemia (glycolysis, polyol hexоzamine pathways) glyoxal, methylglyoxal, active forms glucose. question advanced glycation end (AGEs) oxidation protein (AOРР) remains controversial. assumed AGEs AOРР levels depend on severity syndrome.

Language: Английский

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Antiglycoxidative properties of amantadine – a systematic review and comprehensive in vitro study

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 38(1), P. 138 - 155

Published: Nov. 2, 2022

An important drug used in the treatment of Parkinson's disease is amantadine. We are first to perform a comprehensive study based on various glycation and oxidation factors, determining impact amantadine protein glycoxidation. Sugars (glucose, fructose, galactose) aldehydes (glyoxal, methylglyoxal) were as agents, chloramine T was an oxidant. Glycoxidation biomarkers albumin treated with generally not different from control group (glycation/oxidation factors), indicating that did affect processes. Molecular docking analysis reveal strong binding sites bovine serum structure. Although poorly scavenged hydroxyl radical hydrogen peroxide, it had significantly lower antioxidant antiglycation effect than all inhibitors. In some cases, even demonstrated glycoxidant, proglycation, prooxidant properties. summary, exhibited weak properties lack activity.

Language: Английский

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Modulatory Effect of Fermented Black Soybean and Adlay on Gut Microbiota Contributes to Healthy Aging

Molecular Nutrition & Food Research, Journal Year: 2023, Volume and Issue: 67(5)

Published: Jan. 19, 2023

Aging is a natural process characterized by multifactorial, physical decline, and functional disability. Nevertheless, healthy aging can be achieved following multidirectional strategy. The current study aims to investigate the anti-aging potential of fermented black soybean adlay (FBA).FBA supplements are incorporated into mouse model that designed evaluate effects. Results show FBA supplementation prevents muscle loss visceral adipose tissue accumulation. also reduce biomarkers (including expression hepatic p16INK4A galactosidase beta-1 (GLB1). Hepatic 8-hydoxy-2'-deoxyguanosine (8-oxodG) pro-inflammatory cytokines have been significantly reduced. Lastly, improves aging-related gut microbial dysbiosis reshaping composition promoting growth beneficial microbes such as Alistipes, Anaeroplasma, Coriobacteriaceae UCG002, Parvibacter members in both genders aged mice. In prediction microbiota, correlations metabolic, neurodegenerative, infectious, immune system diseases reduced supplemented mice compared Moreover, reverse ability microbiota for lipid metabolism xenobiotics biodegradation.The results suggest exhibits noteworthy effects it potentially developed food aging.

Language: Английский

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Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 18

Published: Feb. 25, 2022

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects normoxia and hypoxia acute exercise. The study aimed at evaluating relationship between enzymatic nonenzymatic antioxidant barrier, total antioxidant/oxidant status, nitrosative damage, inflammation, lysosomal function in different exercise protocols under hypoxia. Fifteen competitive athletes were recruited for study. They subjected to two types cycling with intensities durations: graded until exhaustion (GE) simulated 30 km individual time trial (TT). Both performed normoxic hypoxic (FiO2 = 16.5%) conditions. number subjects was determined based on our experiment, assuming test power 0.8 α 0.05. We demonstrated enhanced systems (GE: ↑ catalase (CAT), superoxide dismutase; TT: CAT) concomitant decrease plasma reduced glutathione. In exercising hypoxia, redox status shifted favor oxidation reactions oxidant ↓ ratio), leading increased oxidation/nitration proteins advanced protein products (AOPP), ischemia-modified albumin, 3-nitrotyrosine, S-nitrosothiols; AOPP) lipids malondialdehyde). Concentrations nitric oxide its metabolites (peroxynitrite) significantly higher exercisers an associated increase inflammatory mediators myeloperoxidase, tumor necrosis factor-alpha) exoglycosidase activity N-acetyl-β-hexosaminidase, β-glucuronidase). Our indicates that even single intensive session disrupts barrier leads damage systemic level. High-intensity alters homeostasis more than less intense (TT, near anaerobic threshold) longer duration (20.2 ± 1.9 min vs. 61.1 5.4 min-normoxia; 18.0 63.7 3.0 min-hypoxia), while exacerbates stress, dysfunction athletic subjects.

Language: Английский

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Malondialdehyde levels in diabetic retinopathy patients: a systematic review and meta-analysis

Chinese Medical Journal, Journal Year: 2023, Volume and Issue: unknown

Published: April 27, 2023

Abstract Background: It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared MDA and without DR. Methods: The authors searched PubMed, Medline (Ovid), Embase Web of Science for case-control studies conducted before May 2022 English that following MeSH search terms were used: (“malondialdehyde” or “thiobarbituric acid reactive substances (TBARS)” “lipid peroxidation” “oxidative stress”) “diabetic retinopathy.” Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality included studies. Random-effects pairwise meta-analysis pooled effect size standardized mean difference (SMD) 95% confidence intervals (CIs). Results: 29 1680 DR 1799 diabetes but not Compared DR, higher those (SMD, 0.897; CI, 0.631 1.162; P < 0.001). study did identify credible subgroup effects publication bias sensitivity analysis confirmed robustness study. Conclusions: Circulating are without. Future comparative use more specific methods required draw firm conclusions. Registration: PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022352640.

Language: Английский

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