Viral infection may represent a stress condition to the host cell. Cells react to it by triggering the defence programme to restore homeostasis and these events may in turn impact the viral replication. The knowledge about tick-borne encephalitis virus (TBEV) infection-associated stress is limited. Here we investigated the interplay between TBEV infection and stress pathways in PMJ2-R mouse macrophage cell line, as macrophages are the target cells in early phases of TBEV infection. First, to determine how stress influences TBEV replication, the effect of stress inducers H2O2 and tunicamycin (TM) was tested. Viral multiplication was decreased in the presence of both stress inducers suggesting that the stress and cellular stress responses restrict the virus replication. Second, we investigated the induction of oxidative stress and endoplasmic reticulum (ER) stress upon TBEV infection. The level of oxidative stress was interrogated by measuring the reactive oxygen species (ROS). ROS were intermittently increased in infected cells at 12 hpi and at 72 hpi. As mitochondrial dysfunction may result in increased ROS level, we evaluated the mitochondrial homeostasis by measuring the mitochondrial membrane potential (MMP) and found that TBEV infection induced the hyperpolarization of MMP. Moreover, a transient increase of gene expression of stress-induced antioxidative enzymes, like p62, Gclm and Hmox1, was detected. Next, we evaluated the ER stress upon TBEV infection by analysing unfolded protein responses (UPR). We found that infection induced gene expression of two general sensors BiP and CHOP and activated the IRE1 pathway of UPR. Finally, since the natural transmission route of TBEV from its tick vector to the host is mediated via tick saliva, the impact of tick saliva from Ixodes ricinus on stress pathways in TBEV-infected cells was tested. We observed only marginal potentiation of UPR pathway. In conclusion, we found that TBEV infection of PMJ2-R cells elicits the changes in redox balance and triggers cellular stress defences, including antioxidant responses and the IRE1 pathway of UPR. Importantly, our results revealed the negative effect of stress-evoked events on TBEV replication and only marginal impact of tick saliva on stress cellular pathways.
- MeSH
- buněčné linie MeSH
- klíšťová encefalitida * MeSH
- myši MeSH
- peroxid vodíku metabolismus MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.
- MeSH
- buněčná diferenciace * účinky léků MeSH
- buňky Th17 * imunologie metabolismus MeSH
- Chlamydophila psittaci * MeSH
- dospělí MeSH
- interleukin-1beta * metabolismus MeSH
- kaspasa 1 * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- peroxid vodíku metabolismus MeSH
- protein NLRP3 * metabolismus MeSH
- psitakóza MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- regulační T-lymfocyty * imunologie MeSH
- signální transdukce MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.
- MeSH
- anthokyaniny metabolismus farmakologie MeSH
- antioxidancia * farmakologie metabolismus MeSH
- chronická nemoc MeSH
- kyselina peroxydusitá farmakologie MeSH
- lidé MeSH
- nádory * MeSH
- oxid dusnatý MeSH
- oxidační stres MeSH
- peroxid vodíku MeSH
- reaktivní formy kyslíku metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- superoxidy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Crohn's disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of the DUOX2 gene. The protein product of the DUOX2 gene is a dual oxidase enzyme producing H2O2 in the bowel. Reduced H2O2 levels impact mucosal homeostasis and contribute to the development of inflammatory bowel disease. Thus far, only 19 patients with IBD with the DUOX2 variants have been described. METHODS: Here we present a case report of an adolescent female diagnosed at eleven years of age with IBD that was subsequently reclassified as Crohn's disease. She was treated with immunosuppressants and biological therapy but experienced additional complications. Her peripheral blood lymphocyte DNA was studied using massive parallel sequencing. Detected variants were functionally studied. RESULTS: Whole exome sequencing found two novel DUOX2 gene variants: a de novo variant c.3646C>T; p.R1216W and a maternally inherited variant c.3391G>A; p.A1131T which were initially classified as variants of unknown significance. However, follow-up functional studies demonstrated that both DUOX2 variants led to impaired H2O2 generation, which led to their reclassification to the likely pathogenic class according to the ACMG.net. Therefore, we conclude that these variants are causative for the disease. CONCLUSIONS: Identifying novel variants in patients with Crohn's disease and their families is important for precision medicine approaches and understanding of the pathogenesis of likely "monogenic" rare forms of inflammatory bowel disease.
- MeSH
- Crohnova nemoc * genetika MeSH
- duální oxidázy genetika MeSH
- idiopatické střevní záněty * genetika MeSH
- lidé MeSH
- mladiství MeSH
- peroxid vodíku MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
The innate immune response represents the first-line of defense against invading pathogens. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in various aspects of innate immune function, which involves respiratory bursts and inflammasome activation. These reactive species widely distributed within the cellular environment are short-lived intermediates that play a vital role in cellular signaling and proliferation and are likely to depend on their subcellular site of formation. NADPH oxidase complex of phagocytes is known to generate superoxide anion radical (O2•-) that functions as a precursor for antimicrobial hydrogen peroxide (H2O2) production, and H2O2 is utilized by myeloperoxidase (MPO) to generate hypochlorous acid (HOCl) that mediates pathogen killing. H2O2 modulates the expression of redox-responsive transcriptional factors, namely NF-kB, NRF2, and HIF-1, thereby mediating redox-based epigenetic modification. Survival and function of immune cells are under redox control and depend on intracellular and extracellular levels of ROS/RNS. The current review focuses on redox factors involved in the activation of immune response and the role of ROS in oxidative modification of proteins in macrophage polarization and neutrophil function.
Coronary heart disease (CHD) is one of the most commonly seen cardiovascular conditions across the globe. Junctional cadherin 5 associated (JCAD) protein is found in the intercellular junctions of endothelial cells and linked to cardiovascular diseases. Nonetheless, the influence of JCAD on cardiomyocyte injury caused by CHD is unclear. A model of H2O2-induced H9c2 cell injury was constructed, and JCAD mRNA and protein levels were assessed by qRT-PCR and Western blot. The impacts of JCAD on the proliferation or apoptosis of H9c2 cells were explored by CCK-8 assay, Western blot and TUNEL staining. The effect of JCAD on the inflammatory response and vascular endothelial function of H9c2 cells was detected using ELISA kits. The levels of Wnt/β-catenin pathway-related proteins were assessed by Western blot. H2O2 treatment led to a rise in the levels of JCAD in H9c2 cells. Over-expression of JCAD promoted H2O2-induced cellular injury, leading to notably elevated contents of inflammatory factors, along with vascular endothelial dysfunction. In contrast to over-expression of JCAD, silencing of JCAD attenuated H2O2-induced cellular injury and inhibited apoptosis, inflammatory response and vascular endothelial dysfunction. Notably, JCAD could regulate the Wnt/β-catenin pathway, while DKK-1, Wnt/β-catenin pathway antagonist, counteracted the enhancing impact of JCAD over-expression on H2O2-induced H9c2 cell injury, further confirming that JCAD acts by regulating the Wnt/β-catenin pathway. In summary, over-expression of JCAD promoted H2O2-induced H9c2 cell injury by activating the Wnt/β-catenin pathway, while silencing of JCAD attenuated the H2O2-induced cell injury.
- MeSH
- apoptóza * účinky léků MeSH
- beta-katenin metabolismus MeSH
- buněčné linie MeSH
- down regulace * účinky léků MeSH
- kadheriny metabolismus MeSH
- kardiomyocyty * metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- peroxid vodíku * farmakologie MeSH
- proliferace buněk účinky léků MeSH
- signální dráha Wnt * účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Oxidored-nitro domain-containing protein 1 (NOR1) is a critical tumour suppressor gene, though its regulatory mechanism in oxidative stress of glioblastoma (GBM) remains unclear. Hence, further study is needed to unravel the function of NOR1 in the progression of oxidative stress in GBM. In this study, we evaluated the expression of NOR1 and nuclear respiratory factor 1 (NRF1) in GBM tissue and normal brain tissue (NBT) using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and investigated their relationship. We then induced oxidative stress in U251 cells through H2O2 treatment and conducted Cell Count-ing Kit-8, Transwell and wound healing assays to analyse cell proliferation, invasion and migration. Cell apoptosis was assessed by flow cytometry and TUNEL staining. We also measured the activities of superoxide dismutase and catalase, as well as the level of reactive oxygen species (ROS) using biochemical techniques. Via qRT-PCR and WB, the mRNA and protein expression levels of NOR1 and NRF1 were determined. Chromatin immunoprecipitation (ChIP) assays were applied to validate NRF1's interaction with NOR1. Our results showed that the expression of NOR1 and NRF1 was low in GBM, and their expression levels were positively correlated. H2O2-induced oxidative stress reduced NRF1 and NOR1 expression levels and increased the ROS level. The ChIP assay confirmed the binding of NRF1 to NOR1. Over-expression of NRF1 attenuated the inhibitory effect of oxidative stress on the proliferation, migration and invasion of U251 cells, which was reversed by knockdown of NOR1.
- MeSH
- glioblastom * genetika MeSH
- lidé MeSH
- oxidační stres MeSH
- peroxid vodíku farmakologie MeSH
- proliferace buněk MeSH
- reaktivní formy kyslíku MeSH
- transkripční faktor NRF1 * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Three basil plant varieties (Ocimum basilicum var. Genovese, Ocimum × citriodorum, and Ocimum basilicum var. purpurascens) were grown under moderate light (about 300 μmol photons m-2 s-1) in a glasshouse or growth chamber and then either transferred to an open field (average daily dose: 29.2 kJ m-2 d-1) or additionally exposed to UV-B irradiation in a growth chamber (29.16 kJ m-2 d-1), to reveal the variety-specific and light-specific acclimation responses. Total antioxidant capacity (TAC), phenolic profile, ascorbate content, and class III peroxidase (POD) activity were used to determine the antioxidant status of leaves under all four light regimes. Exposure to high solar irradiation at the open field resulted in an increase in TAC, total hydroxycinnamic acids (HCAs, especially caffeic acid), flavonoids, and epidermal UV-absorbing substances in all three varieties, as well as a two-fold increase in the leaf dry/fresh weight ratio. The supplemental UV-B irradiation induced preferential accumulation of HCAs (rosmarinic acid) over flavonoids, increased TAC and POD activity, but decreased the ascorbate content in the leaves, and inhibited the accumulation of epidermal flavonoids in all basil varieties. Furthermore, characteristic leaf curling and UV-B-induced inhibition of plant growth were observed in all basil varieties, while a pro-oxidant effect of UV-B was indicated with H2O2 accumulation in the leaves and spotty leaf browning. The extent of these morphological changes, and oxidative damage depended on the basil cultivar, implies a genotype-specific tolerance mechanism to high doses of UV-B irradiation.
The use of microbial enzymes is highly encouraged in paper and pulp industries to reduce the excessive use of hazardous chemicals. During the study, xylanase of Bacillus stratosphericus EB-11 was characterized for pulp bleaching applications. The extracellular xylanase was produced under submerged fermentation using bamboo waste as a natural carbon source. There was fast cell division and enzyme production under optimized fermentation conditions in the bioreactor. The highest activity was 91,200U after 30 h of growth with Km and Vmax of 3.52 mg/mL and 391.5 μmol/min per mg respectively. The purified enzyme with molecular mass ~ 60 kDa had conferred positive activity on native PAGE. The strong inhibition by ethylenediaminetetraacetate and SDS showed the metallo-xylanase nature of the purified enzyme. The bacterial xylanase reduces the use of hydrogen peroxide by 0.4%. Similarly, biological oxygen demand and chemical oxygen demand were reduced by 42.6 and 35.2%. The xylanase-hydrogen peroxide combined treatment and conventional chlorine dioxide-alkaline (CDE1D1D2) bleaching showed almost similar improvement in physicochemical properties of bamboo pulp. Xylanase-peroxide bleaching reduces the lignin content to 4.95% from 13.32% unbleached pulp. This content after CDE1D1D2 treatment was 4.21%. The kappa number decreased from 15.2 to 9.46 with increasing the burst factor (15.51), crystallinity index (60.25%), viscosity (20.1 cp), and brightness (65.4%). The overall finding will encourage the development of new cleaner methods of bleaching in the paper and pulp industry.
- MeSH
- Bacillus * MeSH
- endo-1,4-beta-xylanasy MeSH
- lignin chemie MeSH
- peroxid vodíku MeSH
- sloni * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H2O2) is an important ROS entity and plays a crucial role in several physiological processes, including cell differentiation, cell signalling, and apoptosis. However, excessive production of H2O2 has been shown to disrupt biomolecules and cell organelles, leading to an inflammatory response and contributing to the development of health complications such as collagen deposition, aging, liver fibrosis, sepsis, ulcerative colitis, etc. Extracts of different plant species, phytochemicals, and Lactobacillus sp (probiotic) have been reported for their anti-oxidant potential. In this view, the researchers have gained significant interest in exploring the potential plants spp., their phytochemicals, and the potential of Lactobacillus sp. strains that exhibit anti-oxidant properties and health benefits. Thus, the current review focuses on comprehending the information related to the formation of H2O2, the factors influencing it, and their pathophysiology imposed on human health. Moreover, this review also discussed the anti-oxidant potential and role of different extract of plants, Lactobacillus sp. and their fermented products in curbing H2O2‐induced oxidative stress in both in-vitro and in-vivo models via boosting the anti-oxidative activity, inhibiting of important enzyme release and downregulation of cytochrome c, cleaved caspases-3, - 8, and - 9 expression. In particular, this knowledge will assist R&D sections in biopharmaceutical and food industries in developing herbal medicine and probiotics-based or derived food products that can effectively alleviate oxidative stress issues induced by H2O2 generation.
- MeSH
- antioxidancia * farmakologie metabolismus MeSH
- apoptóza MeSH
- lidé MeSH
- oxidační stres MeSH
- peroxid vodíku farmakologie MeSH
- probiotika * farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rostliny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
