Betaine Ameliorates Brain Damage in a Rat Model of Ischemia/Reperfusion Injury

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.

HprSR is a Reactive Chlorine Species-Sensing, Two-Component System in Escherichia coli

Two-component systems (TCS) are signalling pathways that allow bacterial cells to sense, respond and adapt to fluctuating environments. Among the classical TCS of Escherichia coli , HprSR has recently been shown to be involved in the regulation of msrPQ , which encodes the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of msrPQ in an HprSR-dependant manner, whereas H 2 O 2 , NO and paraquat (a superoxide generator) do not. Therefore, HprS appears to be an HOCl-sensing histidine kinase. Using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HprS are important for its activity: as HOCl preferentially oxidizes Met residues, we provide evidence that HprS could be activated via the reversible oxidation of its methionine residues, meaning that MsrPQ plays a role in switching HprSR off. We propose that the activation of HprS by HOCl could occur through a Met redox switch. HprSR appears to be the first characterized TCS able to detect reactive chlorine species (RCS) in E. coli . This study represents an important step towards understanding the mechanisms of RCS resistance in prokaryotes. IMPORTANCE Understanding how bacteria respond to oxidative stress at the molecular level is crucial in the fight against pathogens. HOCl is one of the most potent industrial and physiological microbiocidal oxidants. Therefore bacteria have developed counterstrategies to survive HOCl-induced stress. Over the last decade, important insights into these bacterial protection factors have been obtained. Our work establishes HprSR as a reactive chlorine species-sensing, two-component system in Escherichia coli MG1655, which regulates the expression of MsrPQ, a repair system for HOCl-oxidized proteins. Moreover we provide evidence suggesting that HOCl could activate HprS through a methionine redox switch.

Metabolomic Profiles Associated With Incident Ischemic Stroke

Background:Women have higher lifetime risk of stroke than men, and metabolic factors seem more strongly associated with stroke for women than men. However, few studies in either men or women have evaluated metabolomic profiles and incident stroke.Methods:We applied liquid chromatography-tandem mass spectrometry to measure 519 plasma metabolites in a discovery set of women in the Nurses’ Health Study ([NHS], 454 incident ischemic stroke cases, 454 controls) with validation in two independent, prospective cohorts: Prevención con Dieta Mediterránea ([PREDIMED], 118 stroke cases, 791 controls), and Nurses’ Health Study 2 ([NHS2], 49 ischemic stroke cases, 49 controls). We applied logistic regression models with stroke as the outcome to adjust for multiple risk factors; the false discovery rate (FDR) was controlled through the q value method.Results:Twenty-three metabolites were significantly associated with incident stroke in NHS after adjustment for traditional risk factors (q value <0.05). Of these, 14 metabolites were available in PREDIMED and 3 were significantly associated with incident stroke: methionine sulfoxide, N6-acetyllysine, and sucrose (q value<0.05). In NHS2, one of the 23 metabolites (glucuronate) was significantly associated with incident stroke (q value <0.05). For all four metabolites, higher levels were associated with increased risk. These four metabolites were used to create a stroke metabolite score (SMS) in the NHS and tested in PREDIMED. Per unit of standard deviation of SMS, the odds ratio for incident stroke was 4.12 (95% CI: 2.26 – 7.51) in PREDIMED, after adjustment for risk factors. In PREDIMED, the area under the ROC curve (AUC) for the model including SMS and traditional risk factors was 0.70 (95% CI: 0.75-0.79) versus the AUC for the model including the traditional risk factors only of 0.65 (95% CI: 0.70-75), corresponding to a 5% improvement in risk prediction with SMS (p < 0.005).Discussion:Metabolites associated with stroke included two amino acids, a carboxylic acid and sucrose. A composite SMS including these metabolites was associated with ischemic stroke and showed improvement in risk prediction beyond traditional risk factors.Classification of Evidence:This study provides Class II evidence that a stroke metabolic score accurately predicts incident ischemic stroke risk.

Kinetic regularities of electrochemical oxidation of the methionine anion on platinated platinum

The purpose of this study was the determination of the kinetic regularities of the methionine electrooxidation process on the Pt(Pt) electrode in an aqueous-alkaline medium.The main kinetic regularities of the methionine anion electrooxidation process were determined using by the methods of cyclic voltammetry, coulometry, and electrochemical impedance spectroscopy. The concentration of methionine in the alkaline solution before and after anodic oxidation was determined spectrophotometrically using spectrophotometer UNICO 2800. The measurements were carried out at room temperature both in an argon atmosphere and in an aerated aqueous solution. The results of voltammetric measurements were adjusted for the limiting oxygen recovery current and the charging current of the double electric layer.The range of potentials of the electrochemical activity of the methionine anion on the Pt(Pt) electrode, the number of electrons involved in the anode process, and its kinetic scheme were determined. The main product of the electrooxidation of methionine in an alkaline medium on Pt(Pt) was the methionine sulfoxide anion. It was shown that the electrooxidation of the methionine anion on Pt (Pt) was carried out from the adsorbed state and was irreversible.

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.e., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.e., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks. Methods Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit. Results We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks. Conclusions It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation.