We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.

• MeSH
• beta-buňky metabolismus   patologie   sekrece   MeSH
• homeostáza * MeSH
• inzulin sekrece   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Significance: Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane. Its non-invaginated part, the inner boundary membrane (IBM) forms a cylindrical sandwich with the outer mitochondrial membrane (OMM). Crista membranes (CMs) meet IBM at crista junctions (CJs) of mt cristae organizing system (MICOS) complexes connected to OMM sorting and assembly machinery (SAM). Cristae dimensions, shape, and CJs have characteristic patterns for different metabolic regimes, physiological and pathological situations. Recent Advances: Cristae-shaping proteins were characterized, namely rows of ATP-synthase dimers forming the crista lamella edges, MICOS subunits, optic atrophy 1 (OPA1) isoforms and mitochondrial genome maintenance 1 (MGM1) filaments, prohibitins, and others. Detailed cristae ultramorphology changes were imaged by focused-ion beam/scanning electron microscopy. Dynamics of crista lamellae and mobile CJs were demonstrated by nanoscopy in living cells. With tBID-induced apoptosis a single entirely fused cristae reticulum was observed in a mitochondrial spheroid. Critical Issues: The mobility and composition of MICOS, OPA1, and ATP-synthase dimeric rows regulated by post-translational modifications might be exclusively responsible for cristae morphology changes, but ion fluxes across CM and resulting osmotic forces might be also involved. Inevitably, cristae ultramorphology should reflect also mitochondrial redox homeostasis, but details are unknown. Disordered cristae typically reflect higher superoxide formation. Future Directions: To link redox homeostasis to cristae ultramorphology and define markers, recent progress will help in uncovering mechanisms involved in proton-coupled electron transfer via the respiratory chain and in regulation of cristae architecture, leading to structural determination of superoxide formation sites and cristae ultramorphology changes in diseases. Antioxid. Redox Signal. 39, 635-683.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• homeostáza MeSH
• mitochondriální membrány * metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• oxidace-redukce MeSH
• superoxidy * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Polyethylenimines (PEIs) are among the most efficient polycationic non-viral transfectants. PEI architecture and size not only modulate transfection efficiency, but also cytotoxicity. However, the underlying mechanisms of PEI-induced multifaceted cell damage and death are largely unknown. Here, we demonstrate that the central mechanisms of PEI architecture- and size-dependent perturbations of integrated cellular metabolomics involve destabilization of plasma membrane and mitochondrial membranes with consequences on mitochondrial oxidative phosphorylation (OXPHOS), glycolytic flux and redox homeostasis that ultimately modulate cell death. In comparison to linear PEI, the branched architectures induced greater plasma membrane destabilization and were more detrimental to glycolytic activity and OXPHOS capacity as well as being a more potent inhibitor of the cytochrome c oxidase. Accordingly, the branched architectures caused a greater lactate dehydrogenase (LDH) and ATP depletion, activated AMP kinase (AMPK) and disturbed redox homeostasis through diminished availability of nicotinamide adenine dinucleotide phosphate (NADPH), reduced antioxidant capacity of glutathione (GSH) and increased burden of reactive oxygen species (ROS). The differences in metabolic and redox imprints were further reflected in the transfection performance of the polycations, but co-treatment with the GSH precursor N-acetyl-cysteine (NAC) counteracted redox dysregulation and increased the number of viable transfected cells. Integrated biomembrane integrity and metabolomic analysis provides a rapid approach for mechanistic understanding of multifactorial polycation-mediated cytotoxicity, and could form the basis for combinatorial throughput platforms for improved design and selection of safer polymeric vectors.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• antioxidancia metabolismus   farmakologie   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• buněčné dýchání účinky léků   MeSH
• buněčné linie MeSH
• energetický metabolismus účinky léků   MeSH
• glutathion metabolismus   MeSH
• homeostáza MeSH
• kinetika MeSH
• lidé MeSH
• mitochondriální membrány účinky léků   metabolismus   MeSH
• molekulární struktura MeSH
• molekulová hmotnost MeSH
• oxidace-redukce MeSH
• oxidační stres účinky léků   MeSH
• polyethylenimin chemie   toxicita   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• spotřeba kyslíku účinky léků   MeSH
• transfekce metody   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

• MeSH
• antioxidancia metabolismus   MeSH
• apoptóza MeSH
• dieta MeSH
• homeostáza MeSH
• krmivo pro zvířata analýza   MeSH
• kur domácí * metabolismus   MeSH
• lidé MeSH
• oxidace-redukce MeSH
• potravní doplňky MeSH
• T-2 toxin * toxicita   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Redox status is a key determinant in the fate of β-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. β-cells require proper redox signaling already in cell ontogenesis during the development of mature β-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional β-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of β-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged β-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact β-cell redox homeostasis and establish prooxidative metabolism. This can further affect β-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target β-cells leading to their dedifferentiation, dysfunction and eventually cell death.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

To maintain the activity of meristems is an absolute requirement for plant growth and development, and the role of the plant hormones auxin and cytokinin in apical meristem function is well established. Only little attention has been given, however, to the function of the reactive oxygen species (ROS) gradient along meristematic tissues and its interplay with hormonal regulatory networks. The interdependency between auxin-related, cytokinin-related and ROS-related circuits controls primary growth and development while modulating plant morphology in response to detrimental environmental factors. Because ROS interaction with redox-active compounds significantly affects the cellular redox gradient, the latter constitutes an interface for crosstalk between hormone and ROS signalling pathways. This review focuses on the mechanisms underlying ROS-dependent interactions with redox and hormonal components in shoot and root apical meristems which are crucial for meristems maintenance when plants are exposed to environmental hardships. We also emphasize the importance of cell type and the subcellular compartmentalization of ROS and redox networks to obtain a holistic understanding of how apical meristems adapt to stress.

• MeSH
• cytokininy metabolismus   MeSH
• homeostáza MeSH
• kyseliny indoloctové metabolismus   MeSH
• oxidace-redukce MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• vývoj rostlin * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Úvod: Dutina ústní představuje komplexní systém, kde probíhá vzájemná chemická komunikace mezi tkáněmi, mikrobiotou a složkami sliny a potravy. Tento článek je zaměřen na hormetické efekty a elektrofilní sloučeniny, které mohou hrát roli v obranných mechanismech proti oxidačnímu stresu a zánětlivým procesům. Hormetické efekty, vyvolané subletálními nebo subtoxickými stresory, mohou aktivovat reparační mechanismy a posílit odolnost tkání proti poškození. Metodika: Analýza byla provedena prostřednictvím vyhledávání ve třech elektronických databázích: Web of Science, PubMed a Scopus. V rámci rešerše jsme se soustředili na studie publikované mezi lety 2000 a 2023, které se zabývaly oxidačně-redukčními procesy, zánětlivými stavy a aktivací Nrf2 dráhy v ústní dutině. Vyloučeny byly studie zaměřené na nádorová onemocnění. Závěr: Elektrofilní sloučeniny působí jako jeden z činitelů zasahujících do homeostázy dutiny ústní a mohou tak představovat terapeutický potenciál v zubním lékařství, konkrétně v parodontologii. Zjištění založená na in vitro a preklinických studiích však vyžadují další ověření v klinických podmínkách, přičemž je třeba zvážit i interakce s orální mikrobiotou.

Introduction: The oral cavity is a complex system in which mutual chemical communication occurs between tissues, microbiota, and components of saliva and food. This paper focuses on hormetic effects and electrophilic compounds, which can play a role in defense mechanisms against oxidative stress and inflammatory processes. Hormetic effects, induced by sublethal or subtoxic stressors, can activate repair mechanisms and enhance tissue resistance to damage. Methods: The analysis was conducted through searches in three electronic databases: Web of Science, PubMed, and Scopus. Our research focused on studies published between 2000 and 2023 that dealt with redox processes, inflammatory conditions, and activation of the Nrf2 pathway in the oral cavity. Studies focused on cancerous diseases were excluded. Conclusion: Electrophilic compounds act as one of the agents that interfere with the homeostasis of the oral cavity, and can thus find therapeutic potential in dentistry, specifically in periodontology. However, findings based on in vitro and preclinical studies require further verification under clinical conditions, and also considering interactions with oral microbiota.

• MeSH
• antioxidační responzivní elementy * fyziologie   MeSH
• fyziologický stres MeSH
• homeostáza fyziologie   MeSH
• hormeze fyziologie   MeSH
• lidé MeSH
• metabolické sítě a dráhy MeSH
• oxidace-redukce MeSH
• ústa * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• systematický přehled MeSH

Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behavior in normal and malignant hematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPCs. We defined the redox state of 4,438 cysteines in fetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in fetal HSPCs. Our data identified ontogenic changes to oxidation state of thiols in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified oxidation changes to thiols acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in fetal HSPCs. Our data has demonstrated that redox signaling contributes to the regulation of fundamental processes of developmental hematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukemia.

• MeSH
• cystein metabolismus   MeSH
• hematopoéza MeSH
• myši MeSH
• oxidace-redukce MeSH
• proteom * metabolismus   MeSH
• proteomika * MeSH
• sulfhydrylové sloučeniny MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Under normal conditions, the cellular redox status is maintained in a steady state by reduction and oxidation processes. These redox alterations in the cell are mainly sensed by protein thiol residues of cysteines thus regulating protein function. The imbalance in redox homeostasis may therefore regulate protein turnover either directly by redox modulating of transcription factors or indirectly by the degradation of damaged proteins due to oxidation. A new analytical method capable of simultaneously assessing cellular protein expression and cysteine oxidation would provide a valuable tool for the field of cysteine-targeted biology. Here, we show a workflow based on protein quantification using metabolic labeling and determination of cysteine oxidation using reporter ion quantification. We applied this approach to determine protein and redox changes in cells after 5-min, 60-min and 32-h exposure to H2O2, respectively. Based on the functional analysis of our data, we confirmed a biological relevance of this approach and its applicability for parallel mapping of cellular proteomes and redoxomes under diverse conditions. In addition, we revealed a specific pattern of redox changes in peroxiredoxins in a short time-interval cell exposure to H2O2. Overall, our present study offers an innovative, versatile experimental approach to the multifaceted assessment of cellular proteome and its redox status, with broad implications for biomedical research towards a better understanding of organismal physiology and diverse disease conditions.

• MeSH
• chromatografie kapalinová MeSH
• cystein metabolismus   MeSH
• oxidace-redukce * MeSH
• oxidační stres MeSH
• peroxid vodíku metabolismus   MeSH
• peroxiredoxiny metabolismus   MeSH
• proteom * MeSH
• proteomika * metody   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids. An imbalance between the formation of free radicals and their elimination by antioxidant defense systems is termed oxidative stress. Most vulnerable to free radical attack is the cell membrane which may undergo enhanced lipid peroxidation, finally producing mutagenic and carcinogenic malondialdehyde and 4-hydroxynonenal and other exocyclic DNA adducts. While redox-active iron (Fe) and copper (Cu) undergo redox-cycling reactions, for a second group of redox-inactive metals such as arsenic (As) and cadmium (Cd), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. While arsenic is known to bind directly to critical thiols, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. Redox-inert zinc (Zn) is the most abundant metal in the brain and an essential component of numerous proteins involved in biological defense mechanisms against oxidative stress. The depletion of zinc may enhance DNA damage by impairing DNA repair mechanisms. Intoxication of an organism by arsenic and cadmium may lead to metabolic disturbances of redox-active copper and iron, with the occurrence of oxidative stress induced by the enhanced formation of ROS/RNS. Oxidative stress occurs when excessive formation of ROS overwhelms the antioxidant defense system, as is maintained by antioxidants such as ascorbic acid, alpha-tocopherol, glutathione (GSH), carotenoids, flavonoids and antioxidant enzymes which include SOD, catalase and glutathione peroxidase. This review summarizes current views regarding the role of redox-active/inactive metal-induced formation of ROS, and modifications to biomolecules in human disease such as cancer, cardiovascular disease, metabolic disease, Alzheimer's disease, Parkinson's disease, renal disease, blood disorders and other disease. The involvement of metals in DNA repair mechanisms, tumor suppressor functions and interference with signal transduction pathways are also discussed.

• MeSH
• kovy chemie   metabolismus   toxicita   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• nemoc * MeSH
• oxidace-redukce MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• rizikové faktory MeSH
• signální transdukce účinky léků   MeSH
• volné radikály metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH