... DISORDERS (Martin Vejrazka) 13 -- 1 Buffer systems 13 -- 1.1 Hydrogen carbonate buffer 13 -- 2 Regulation ... ... of physiological and metabolic processes 14 -- 2.1 Respiration 14 -- 2.2 Renal regulation of ABE 15 ... ... Diet-derived antioxidants 54 -- 4.4.2 Endogenous antioxidant substrates 57 -- 4.5 Stress response and regulated ... ... 158 -- 7.1 Molecular chaperones 159 -- 7.2 Protein disulfide isomerases 162 -- 7.3 Peptidyl prolyl cis-trans ...
Učební texty Univerzity Karlovy
First edition 241 stran : ilustrace ; 23 cm
- Conspectus
- Patologie. Klinická medicína
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- biochemie
- patologie
- NML Publication type
- učebnice vysokých škol
Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.
- MeSH
- Apoptosis drug effects MeSH
- Cell Death drug effects MeSH
- Endoplasmic Reticulum Chaperone BiP * MeSH
- Interleukin-1beta metabolism genetics MeSH
- Caspase 12 metabolism genetics MeSH
- Microglia drug effects metabolism pathology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Neurons drug effects pathology metabolism MeSH
- Neuroprotective Agents pharmacology therapeutic use MeSH
- Prognosis MeSH
- Heat-Shock Proteins metabolism genetics MeSH
- Resveratrol * pharmacology therapeutic use MeSH
- Endoplasmic Reticulum Stress * drug effects MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Transcription Factor CHOP metabolism genetics MeSH
- Brain Injuries, Traumatic * drug therapy pathology metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Studies of vitality/mortality of cortex cells, as well as of the concentrations of ethylene (ETH), gibberellins (GAs), indolic compounds/auxins (ICs/AUXs) and cytokinins (CKs), were undertaken to explain the hormonal background of kinetin (Kin)-regulated cell death (RCD), which is induced in the cortex of the apical parts of roots of faba bean (Vicia faba ssp. minor) seedlings. Quantification was carried out with fluorescence microscopy, ETH sensors, spectrophotometry and ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC‒MS/MS). The results indicated that Kin was metabolized to the transport form, i.e., kinetin-9-glucoside (Kin9G) and kinetin riboside (KinR). KinR was then converted to cis-zeatin (cZ) in apical parts of roots with meristems, to cis-zeatin riboside (cZR) in apical parts of roots without meristems and finally to cis-zeatin riboside 5'-monophosphate (cZR5'MP), which is indicated to be a ligand of cytokinin-dependent receptors inducing CD. The process may be enhanced by an increase in the amount of dihydrozeatin riboside (DHZR) as a byproduct of the pathway of zeatin metabolism. It seems that crosstalk of ETH, ICs/AUXs, GAs and CKs with the cZR5'MP, the cis-zeatin-dependent pathway, but not the trans-zeatin-dependent pathway, is responsible for Kin-RCD, indicating that the process is very specific and offers a useful model for studies of CD hallmarks in plants.
IL-6 is considered one of the well characterized cytokines exhibiting homeostatic, pro- and anti-inflammatory activities, depending on the receptor variant and the induced intracellular cis- or trans-signaling responses. IL-6-activated pathways are involved in the regulation of cell proliferation, survival, differentiation, and cell metabolism changes. Deviations in IL-6 levels or abnormal response to IL-6 signaling are associated with several autoimmune diseases including IgA nephropathy (IgAN), one of most frequent primary glomerulonephritis worldwide. IgAN is associated with increased plasma concentration of IL-6 and increased plasma concentration of aberrantly galactosylated IgA1 immunoglobulin (Gd-IgA1). Gd-IgA1 is specifically recognized by autoantibodies, leading to the formation of circulating immune complexes (CIC) with nephritogenic potential, since CIC deposited in the glomerular mesangium induce mesangial cells proliferation and glomerular injury. Infection of the upper respiratory or digestive tract enhances IL-6 production and in IgAN patients is often followed by the macroscopic hematuria. This review recapitulates general aspects of IL-6 signaling and summarizes experimental evidences about IL-6 involvement in the etiopathogenesis of IgA nephropathy through the production of Gd-IgA1 and regulation of mesangial cell proliferation.
- MeSH
- Galactose metabolism MeSH
- Glomerular Mesangium metabolism MeSH
- Glomerulonephritis, IGA * metabolism pathology MeSH
- Immunoglobulin A metabolism MeSH
- Interleukin-6 metabolism MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Perinatal exposure to Δ9-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) and the dopamine D2 receptor (Drd2) in perinatal THC-(pTHC) exposed male rats, focusing on the role of DNA methylation analyzed by pyrosequencing. Simultaneously, the molecular and behavioral abnormalities at two different time points (i.e., neonatal age and adulthood) and the potential preventive effect of peripubertal treatment with cannabidiol, a non-euphoric component of Cannabis, were assessed. The DRD2 methylation was also evaluated in a cohort of subjects with schizophrenia. We observed an increase in both Cnr1 and Drd2 mRNA levels selectively in the prefrontal cortex of adult pTHC-exposed rats with a consistent reduction in DNA methylation at the Drd2 regulatory region, paralleled by social withdrawal and cognitive impairment which were reversed by cannabidiol treatment. These adult abnormalities were preceded at neonatal age by delayed appearance of neonatal reflexes, higher Drd2 mRNA and lower 2-arachidonoylglycerol (2-AG) brain levels, which persisted till adulthood. Alterations of the epigenetic mark for DRD2 were also found in subjects with schizophrenia. Overall, reported data add further evidence to the dopamine-cannabinoid interaction in terms of DRD2 and CNR1 dysregulation which could be implicated in the pathogenesis of schizophrenia spectrum disorders, suggesting that cannabidiol treatment may normalize pTHC-induced psychopathology by modulating the altered dopaminergic activity.
- MeSH
- Behavior, Animal drug effects MeSH
- Humans MeSH
- Maternal-Fetal Exchange MeSH
- RNA, Messenger metabolism MeSH
- DNA Methylation drug effects MeSH
- Rats, Sprague-Dawley MeSH
- Prefrontal Cortex drug effects metabolism MeSH
- Receptor, Cannabinoid, CB1 genetics MeSH
- Receptors, Dopamine D2 genetics MeSH
- Gene Expression Regulation drug effects MeSH
- Schizophrenia genetics MeSH
- Pregnancy MeSH
- Dronabinol pharmacology MeSH
- Prenatal Exposure Delayed Effects * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Volný prodej konopných produktů v Evropě vzbuzuje mezi odpovědnými činiteli pozornost, a to jak z hlediska právního postavení těchto výrobků, tak jejich potenciálních rizik. Tyto produkty jsou uváděny na trh jako přípravky s nízkým obsahem THC (tetrahydrokanabinolu), čímž se na ně podle prodejců nevztahují zákony upravující nakládání s omamnými a psychotropními látkami, nebo jako zdroj CBD (kanabidiolu). Tato publi- kace nabízí prvotní nástin situace. Představuje jednotlivé typy dostupných produktů s nízkým obsahem THC, profily jejich uživatelů, související rizika a regulační opatření přijímaná v tomto ohledu v rámci Evropy. V centru pozornosti této práce jsou produkty s nízkým obsahem THC, které mají podobnou formu jako nelegální přípravky z konopí, jako jsou směsi určené ke kouření, oleje a poživatiny. Materiál poukazuje na výzvy pro činitele odpovědné za tvorbu příslušných politik i ty, kdo mají zájem produkty s nízkým obsahem THC uvádět na trh, pokud jde o vymezení právního statutu těchto produktů a regulačních rámců aplikovatelných na jejich prodej.
- MeSH
- Cannabis * MeSH
- Drug and Narcotic Control * legislation & jurisprudence MeSH
- Humans MeSH
- Medical Marijuana supply & distribution MeSH
- Behavior, Addictive prevention & control MeSH
- Dronabinol standards therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Geographicals
- Europe MeSH
Clostridium perfringens forms biofilms and spores that are a source of food contamination. In this study, the antibacterial activities of Lactobacillus plantarum culture supernatants (LP-S), LP-S fractions, and the plant-derived compound epigallocatechin gallate (EG) were evaluated. Specifically, their effects on the viability and biofilm-forming ability of C. perfringens were assessed. Moreover, the expression of quorum sensing-regulated genes associated with the pathogenesis of this microorganism and that of genes involved in biofilm formation was also investigated. The results showed that both EG and the LP-S exerted bactericidal activity against all C. perfringens strains tested. The minimal bactericidal concentration (MBC) of EG was 75 µg/mL for all strains but ranged from 61 to 121 µg of total protein per mL for LP-S. EG exerted only minor effects on biofilm formation, whereas LP-S, particularly its 10 and 30 K fractions, significantly reduced the biofilm-forming ability of all the strains. The antibiofilm activity of LP-S was lost following preincubation with proteases, suggesting that it was mediated by a proteinaceous molecule. The treatment of C. perfringens with either EG or LP-S did not change the transcript levels of two CpAL (C. perfringens quorum-sensing Agr-like system)-related genes, agrB and agrD, which are known to be involved in the regulation of biofilms, suggesting that LP-S exerted its biofilm inhibitory activity downstream of CpAL signaling. In summary, we demonstrated the bactericidal activity of EG and LP-S against C. perfringens and antibiofilm activity of LP-S at a subinhibitory dose. Our results suggested that these compounds can be further explored for food safety applications to control agents such as C. perfringens.
- MeSH
- Biofilms MeSH
- Clostridium perfringens * drug effects genetics MeSH
- Catechin analogs & derivatives pharmacology MeSH
- Culture Media, Conditioned * pharmacology MeSH
- Lactobacillus plantarum * metabolism MeSH
- Gene Expression Regulation, Bacterial drug effects MeSH
- Publication type
- Journal Article MeSH
Vegetative propagation through somatic embryogenesis is an effective method to produce elite varieties and can be applied as a tool to study the response of plants to different stresses. Several studies show that environmental changes during embryogenesis could determine future plant development. Moreover, we previously reported that physical and chemical conditions during somatic embryogenesis can determine the protein, hormone and metabolite profiles, as well as the micromorphological and ultrastructural organization of embryonal masses and somatic embryos. In this sense, phytohormones are key players throughout the somatic embryogenesis process as well as during numerous stress-adaptation responses. In this work, we first applied different high-temperature regimes (30 °C, 4 weeks; 40 °C, 4 days; 50 °C, 5 min) during induction of Pinus radiata D. Don somatic embryogenesis, together with control temperature (23 °C). Then, the somatic plants regenerated from initiated embryogenic cell lines and cultivated in greenhouse conditions were subjected to drought stress and control treatments to evaluate survival, growth and several physiological traits (relative water content, water potential, photosynthesis, stomatal conductance and transpiration). Based on those preliminary results, even more extreme high-temperature regimes were applied during induction (40 °C, 4 h; 50 °C, 30 min; 60 °C, 5 min) and the corresponding cytokinin profiles of initiated embryonal masses from different lines were analysed. The results showed that the temperature regime during induction had delayed negative effects on drought resilience of somatic plants as indicated by survival, photosynthetic activity and water- use efficiency. However, high temperatures for extended periods of time enhanced subsequent plant growth in well-watered conditions. High-temperature regime treatments induced significant differences in the profile of total cytokinin bases, N6-isopentenyladenine, cis-zeatin riboside and trans-zeatin riboside. We concluded that phytohormones could be potential regulators of stress-response processes during initial steps of somatic embryogenesis and that they may have delayed implications in further developmental processes, determining the performance of the generated plants.
- MeSH
- Pinus * MeSH
- Cytokinins MeSH
- Droughts MeSH
- Plant Growth Regulators MeSH
- Temperature MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.
- MeSH
- Anti-Inflammatory Agents pharmacology therapeutic use MeSH
- Antioxidants therapeutic use MeSH
- Apoptosis * drug effects MeSH
- Hemodynamics drug effects MeSH
- Hypertension, Malignant drug therapy enzymology pathology physiopathology MeSH
- Cardiotonic Agents pharmacology therapeutic use MeSH
- Thiobarbituric Acid Reactive Substances metabolism MeSH
- Myocardium pathology MeSH
- NG-Nitroarginine Methyl Ester chemistry pharmacology MeSH
- Oxidation-Reduction MeSH
- Rats, Inbred SHR MeSH
- bcl-2-Associated X Protein metabolism MeSH
- Resveratrol chemistry pharmacology therapeutic use MeSH
- Heart Ventricles drug effects pathology physiopathology MeSH
- Body Weight drug effects MeSH
- Organ Size drug effects MeSH
- Inflammation complications drug therapy MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
