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Takashi Shichita
Inflammation is an essential step for the pathology of ischemic stroke, and is also an important therapeutic target for developing novel therapeutic methods which have a wide therapeutic time window. Since there is no pathogen in the brain, the inflammation will be triggered by some endogenous molecules which are called as danger associated molecular patterns (DAMPs). So far two important DAMPs, high mobility group box 1 (HMGB1) and peroxiredoxin (PRX), have been recently identified in the ischemic brain. HMGB1 exaggerates the disruption of blood brain barrier; on the other hand, PRX activates mononuclear phagocytes and induces the inflammatory cytokine production through the activation of Toll-like receptor 2 (TLR2) and TLR4...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Gianluca Selvaggio, Pedro M B M Coelho, Armindo Salvador
The system (PTTRS) formed by typical 2-Cys peroxiredoxins (Prx), thioredoxin (Trx), Trx reductase (TrxR), and sulfiredoxin (Srx) is central in antioxidant protection and redox signaling in the cytoplasm of eukaryotic cells. Understanding how the PTTRS integrates these functions requires tracing phenotypes to molecular properties, which is non-trivial. Here we analyze this problem based on a model that captures the PTTRS' conserved features. We have mapped the conditions that generate each distinct response to H2O2 supply rates (vsup), and estimated the parameters for thirteen human cell types and for Saccharomyces cerevisiae...
December 21, 2017: Redox Biology
Sarah Stöcker, Michael Maurer, Thomas Ruppert, Tobias P Dick
Hydrogen peroxide (H2O2) acts as a signaling messenger by triggering the reversible oxidation of redox-regulated proteins. It remains unclear how proteins can be oxidized by signaling levels of H2O2 in the presence of peroxiredoxins, which are highly efficient peroxide scavengers. Here we show that the rapid formation of disulfide bonds in cytosolic proteins is enabled, rather than competed, by cytosolic 2-Cys peroxiredoxins. Under the conditions tested, the combined deletion or depletion of cytosolic peroxiredoxins broadly frustrated H2O2-dependent protein thiol oxidation, which is the exact opposite of what would be predicted based on the assumption that H2O2 oxidizes proteins directly...
December 18, 2017: Nature Chemical Biology
Tamás Bárány, Andrea Simon, Gergő Szabó, Rita Benkő, Zsuzsanna Mezei, Levente Molnár, Dávid Becker, Béla Merkely, Endre Zima, Eszter M Horváth
Background: The present study aims to examine the oxidative stress-related activation of poly(ADP-ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Methods: Patients with CHF (n = 20) and age- and body mass index-matched volunteers (n = 15) with a normal heart function were enrolled. C-reactive protein, N-terminal probrain-type natriuretic peptide (pro-BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4-hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP-ribosyl)ation (PARylation), and apoptosis-inducing factor (AIF) translocation were measured in blood samples of fasting subjects...
2017: Oxidative Medicine and Cellular Longevity
Frederick Adam Zeiler, Joseph Donnelly, Peter Smieleweski, David Menon, Peter John Hutchinson, Marek Czosnyka
To compare ICP derived cerebrovascular reactivity indices in their ability to predict 6-month outcome, and to determine/compare critical thresholds related to outcome for each index, in adult non-craniectomized traumatic brain injury (TBI). Using a retrospective cohort of non-decompressive craniectomy (non-DC) TBI patients, we performed univariate and multivariate binary logistic regression outcome analysis of: pressure reactivity index (PRx), pulse amplitude index (PAx) and a newly described index calculated as the Regression coefficient between intracranial pressure (ICP) waveform Amplitude and Cerebral perfusion pressure RAC (CPP)...
December 14, 2017: Journal of Neurotrauma
Rahimah Othman, Goran T Vladisavljević, Elena Simone, Zoltan K Nagy, Richard G Holdich
Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7-34 μm and was controlled by the PRX concentration in the feed solution (15-25 g L-1), antisolvent/solvent volume ratio (5-30), and type of antisolvent (Milli-Q water or 0...
December 6, 2017: Crystal Growth & Design
Dan-Dan Tu, Yi-Lian Zhou, Wen-Bin Gu, Qi-Hui Zhu, Bin-Peng Xu, Zhong-Kai Zhou, Ze-Peng Liu, Cong Wang, Yu-Yin Chen, Miao-An Shu
The peroxiredoxins (Prxs) define a novel and evolutionarily conserved superfamily of peroxidases able to protect cells from oxidative damage by catalyzing the reduction of a wide range of cellular peroxides. Prxs have been identified in prokaryotes as well as in eukaryotes, however, the composition and number of Prxs family members vary in different species. In this study, six Prxs were firstly identified from the mud crab Scylla paramamosain by RT-PCR and RACE methods. Six SpPrxs can be subdivided into three classes: (a) three typical 2-Cys enzymes denominated as Prx1/2, 3, 4, (b) two atypical 2-Cys enzymes known as Prx5-1 and Prx5-2, and (c) a 1-Cys isoform named Prx6...
December 4, 2017: Molecular Immunology
Yogesh Mishra, Michael Hall, Roland Locmelis, Kwangho Nam, Christopher A G Söderberg, Patrik Storm, Neha Chaurasia, Lal Chand Rai, Stefan Jansson, Wolfgang P Schröder, Uwe H Sauer
Peroxiredoxins (Prxs) are vital regulators of intracellular reactive oxygen species levels in all living organisms. Their activity depends on one or two catalytically active cysteine residues, the peroxidatic Cys (CP) and, if present, the resolving Cys (CR). A detailed catalytic cycle has been derived for typical 2-Cys Prxs, however, little is known about the catalytic cycle of 1-Cys Prxs. We have characterized Prx6 from the cyanobacterium Anabaena sp. strain PCC7120 (AnPrx6) and found that in addition to the expected peroxidase activity, AnPrx6 can act as a molecular chaperone in its dimeric state, contrary to other Prxs...
December 7, 2017: Scientific Reports
Frederick Adam Zeiler, Joseph Donnelly, David Menon, Peter Smieleweski, Peter John Hutchinson, Marek Czosnyka
To describe a new continuous index of physiologic measurement in a TBI population, the moving correlation coefficient between intracranial pressure (ICP) pulse amplitude (AMP) and cerebral perfusion pressure (CPP), which we refer to as RAC. We use patient examples of sustained intracranial hypertension, systemic arterial hypotension and plateau waves, as well as the retrospective analysis of 358 non-decompressive craniectomy (DC) traumatic brain injury (TBI) patients with high frequency ICP and ABP data, to explore the relationships of this new index, RAC, with AMP, ICP, CPP, RAP, pressure reactivity index (PRx) and pulse amplitude index (PAx)...
December 6, 2017: Journal of Neurotrauma
Svetlana N Radyuk, William C Orr
<i>Significance:</i> Peroxiredoxins, a family of thiol-associated peroxidases, are purported to play a major role in sensing and managing H2O2 concentrations and transducing peroxide-derived signals. <i>Recent advances:</i> Peroxiredoxins can act as detoxifying factors and impart effects to cells that can be either sparing or suicidal. Advances have been made to address the qualitative changes in peroxiredoxin function in response to quantitative changes in the signal level and to understand how peroxidredoxin activity could be affected by their own substrates...
December 6, 2017: Antioxidants & Redox Signaling
Xiao-Na Mao, Hong-Jing Zhou, Xiao-Jia Yang, Li-Xue Zhao, Xi Kuang, Chu Chen, Dong-Ling Liu, Jun-Rong Du
The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling appears to be a potential therapeutic strategy for neuroinflammatory injury after acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for the treatment of cerebral ischemia, accompanied by regulation of the autoimmune inflammatory response. The present study investigated the neuroprotective effects of Gas and its derivative, Gas-D, with a focus on the potential mechanism associated with inflammatory Prx-Toll-like receptor 4 (TLR4) signaling...
October 31, 2017: Oncotarget
Xiang Wu, Guoyi Gao, Junfeng Feng, Qing Mao, Jiyao Jiang
Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ICP waveform, amplitude of pulse (AMP), the correlation of ICP amplitude and ICP mean (RAP), pressure reactivity index (PRx), ICP and arterial blood pressure (ABP) wave amplitude correlation (IAAC), and so on, can reflect intracranial status, predict prognosis, and can also be used as guidance of proper treatment. However, most of the clinicians focus only on the mean ICP value while ignoring these parameters because of the limitations of the current devices...
October 17, 2017: Journal of Visualized Experiments: JoVE
Atsushi Tamura, Nobuhiko Yui
Niemann-Pick type C (NPC) disease is a fatal metabolic disorder characterized by the lysosomal accumulation of cholesterol. Although 2-hydroxypropyl β-cyclodextrin (HP-β-CD) promotes the excretion of cholesterol and prolongs the life span in animal models of NPC disease, it requires extremely high dose. We developed acid-labile β-CD-based polyrotaxanes (PRXs) comprising multiple β-CDs threaded along a polymer chain capped with acid-cleavable stopper molecules for potentiating therapeutic efficacy of β-CD in NPC disease...
November 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Atsushi Tamura, Moe Ohashi, Kei Nishida, Nobuhiko Yui
In the retinal pigment epithelium of patients with age-related macular degeneration (AMD), excess N-retinylidene-N-retinylethanolamine (A2E), a dimer of all-trans-retinal, accumulats to induce inflammatory cytokine secretion and phototoxic effects. Therefore, the reduction of intracellular A2E is a promising approach for the prevention and treatment of AMD. In this study, acid-labile β-cyclodextrin (β-CD)-threaded polyrotaxanes (PRXs) were synthesized and investigated their effects on the removal of A2E accumulated in retinal pigment epithelium cells (ARPE-19) in comparison to nonlabile PRXs and 2-hydroxypropyl β-CD (HP-β-CD) were examined...
November 9, 2017: Molecular Pharmaceutics
Eun Seon Lee, Chang Ho Kang, Joung Hun Park, Sang Yeol Lee
<b><i>Significance:</i></b> Sessile plants respond to oxidative stress caused by internal and external stimuli by producing diverse forms of enzymatic and non-enzymatic antioxidant molecules. Peroxiredoxins (Prxs) in plants, including the Prx1, Prx5, Prx6, and PrxQ isoforms, constitute a family of antioxidant enzymes and play important functions in cells. Each Prx localizes to a specific subcellular compartment and has a distinct function in the control of plant growth, development, cellular metabolism, and various aspects of defense signaling...
November 7, 2017: Antioxidants & Redox Signaling
Adam M H Young, Mathew R Guilfoyle, Joseph Donnelly, Peter Smielewski, Shruti Agarwal, Marek Czosnyka, Peter J Hutchinson
Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the United States are 57.7 per 100K in the <5 years of age and 23.1 per 100K in the 5-14 years age group. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Historically, TBI management has been guided by clinical examination. This has been assisted progressively by clinical imaging, intracranial pressure (ICP) monitoring, and finally a software that can calculate optimal brain physiology...
December 20, 2017: Pediatric Research
Xunan Hai, Houshuang Zhang, Zhonghua Wang, Haiyan Gong, Jie Cao, Yongzhi Zhou, Jinlin Zhou
Peroxiredoxins (Prxs) are a family of antioxidant enzymes that reduce peroxides in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine dinucleotide phosphate (NADPH) to resist oxidative stress. In this study, we identified and isolated a 2-Cys Prx designated as 'BmTPx-2' from Babesia microti, with a full-length cDNA of 826 bp and an open reading frame of 756 bp, which encodes a 251-amino acid protein. BLAST analysis demonstrated that BmTPx-2 shows the typical features of members of the 2-Cys Prx family, which includes harboring two conserved VCP motifs with Cys(101) and Cys(221) conserved cysteine residues...
2017: Frontiers in Microbiology
Milena B Silva, Ana P D Demasi, Elizabeth F Martinez, Maristane L Goudinho, Joarlene M Soares, José L C Junqueira, Ney S Araujo
OBJECTIVES: The aim of this study was to evaluate peroxiredoxin I (Prx I) participation in the cellular antioxidant response to low-dose X-rays through the analysis of its expression in buccal mucosa cells from patients of different ages following panoramic dental radiography. MATERIALS AND METHODS: Of the 50 patients included in this study, oral mucosa cells from six adults were collected for the immunofluorescence cytological analysis. The other 44 patients, 11 patients aged below 20 years; 22 patients aged between 20 and 50 years; and 11 patients aged above 50 years, were submitted to panoramic dental radiography, and oral mucosa cells were collected for the gene expression analysis before and 1 hour after exposure...
October 23, 2017: Clinical Oral Investigations
Antonio López-Orenes, María C Bueso, Isabel M Párraga-Aguado, Antonio A Calderón, María A Ferrer
Environmental contamination by hazardous heavy metals/metalloids (metal(loid)s) is growing worldwide. To restrict the migration of toxic contaminants, the establishment of a self-sustainable plant cover is required. Plant growth in multi-polluted soils is a challenging issue not only by metal(loid) toxicities, but also by the co-occurrence of other stressors. Dittrichia viscosa is a pioneer Mediterranean species able to thrive in metal(loid)-enriched tailings in semi-arid areas. The aim of the present work was to examine the metabolic adjustments involved in the acclimation responses of this plant to conditions prevailing in mine-tailings during Mediterranean spring and summer...
October 17, 2017: Science of the Total Environment
Frederick A Zeiler, Danilo Cardim, Joseph Donnelly, David K Menon, Marek Czosnyka, Peter Smielewski
The purpose of our study was to explore relationships between transcranial Doppler (TCD) indices of cerebrovascular reactivity and those derived from intracranial pressure (ICP). Goals included: A) confirming previously described co-variance patterns of TCD/ICP indices, and B) describing thresholds for systolic flow index (Sx; correlation between systolic flow velocity [FVs] and cerebral perfusion pressure [CPP]) associated with outcome. In a retrospective cohort of traumatic brain injury (TBI) patients: with TCD and ICP monitoring, we calculated various continuous indices of cerebrovascular reactivity: A) ICP (pressure reactivity index [PRx]: correlation between ICP and mean arterial pressure [MAP]; PAx: correlation between pulse amplitude of ICP [AMP] and MAP; RAC: correlation between AMP and CPP) and B) TCD (mean flow index [Mx]: correlation between mean flow velocity [FVm] and CPP; Mx_a: correlation between FVm and MAP; Sx: correlation between FVs and CPP; Sx_a: correlation between FVs and MAP; Dx: correlation between diastolic flow velocity [FVd] and CPP; Dx_a: correlation between FVd and MAP)...
December 18, 2017: Journal of Neurotrauma
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