Promotes Hydrogen Peroxide Research Articles

Salinity decline promotes growth and harmful blooms of a toxic alga by diverting carbon flow.

Global climate change intensifies the water cycle and makes freshest waters become fresher and vice-versa. But how this change impacts phytoplankton in coastal, particularly harmful algal blooms (HABs), remains poorly understood. Here, we monitored a coastal bay for a decade and found a significant correlation between salinity decline and the increase of Karenia mikimotoi blooms. To examine the physiological linkage between salinity decreases and K. mikimotoi blooms, we compare chemical, physiological and multi-omic profiles of this species in laboratory cultures under high (33) and low (25) salinities. Under low salinity, photosynthetic efficiency and capacity as well as growth rate and cellular protein content were significantly higher than that under high salinity. More strikingly, the omics data show that low salinity activated the glyoxylate shunt to bypass the decarboxylation reaction in the tricarboxylic acid cycle, hence redirecting carbon from CO2 release to biosynthesis. Furthermore, the enhanced glyoxylate cycle could promote hydrogen peroxide metabolism, consistent with the detected decrease in reactive oxygen species. These findings suggest that salinity declines can reprogram metabolism to enhance cell proliferation, thus promoting bloom formation in HAB species like K. mikimotoi, which has important ecological implications for future climate-driven salinity declines in the coastal ocean with respect to HAB outbreaks.

Quorum sensing signal autoinducer-2 promotes hydrogen peroxide degradation in water by Gram-positive bacteria

Hydrogen peroxide is widely used to remedy bacterial and parasitic infections, but its excessive use will cause severe damage to aquatic animals. Moreover, there is no safe, efficient and low-cost method to degrade residual hydrogen peroxide in water. Here we developed a hydrogen peroxide removal mechanism by which autoinducer-2 (AI-2), a quorum sensing signal molecule that can promote the hydrogen peroxide degradation by Gram-positive bacteria. Here, we investigated the promotion effect of AI-2 on hydrogen peroxide degradation by Deinococcus sp. Y35 and the response of the antioxidant system. We further sought to understand the key mechanism underlying the promotion effect of AI-2 on hydrogen peroxide degradation is that, AI-2 contributed to the resistance of strain Y35 to oxidative stress induced by hydrogen peroxide, and altered membrane permeability of strain Y35 that allowed more hydrogen peroxide to enter bacterial cells and be degraded. Additionally, AI-2 can also encourage multiple Gram-positive bacteria to degrade hydrogen peroxide. Accordingly, our study serves as a reference for the regulation mechanism of the signal molecule AI-2 and provides the development of new strategies for hydrogen peroxide degradation.

CO2-activated graphite felt as an effective substrate to promote hydrogen peroxide synthesis and enhance the electro-Fenton activity of graphite/Fe3O4 composites in situ fabricated from acid mine drainage

CO2-activated graphite felt as an effective substrate to promote hydrogen peroxide synthesis and enhance the electro-Fenton activity of graphite/Fe3O4 composites in situ fabricated from acid mine drainage

Iron(III) complexes promote hydrogen peroxide activation for efficient degradation of dyeing wastewater

AbstractCoordination complexes were widely used in advanced oxidation processes. The ligands with various substituents could lead to differences in the catalytic properties and mechanisms. In this work, the iron(III)–N,N′‐dipicolinamide (FeL) complexes (the iron(III) complexes with substituents –CH3, –H, –Cl and –NO2 named as FeL1, FeL2, FeL3 and FeL4, respectively) were used to activate hydrogen peroxide (H2O2) for degrading dyes wastewater. Mechanism studies indicated that the FeL4/H2O2 system contains the FeV=O in addition to the same •OH and O2•− as the other systems, which made it exhibit more excellent performance than others. The results of the performance tests showed that the FeL4/H2O2 system could remove 97%, 89%, 100%, 83%, 100%, and 99% of RR195, RY145, RB194, RB19, MB, and RhB, respectively, which proved the good application performance of the FeL4/H2O2 system. In addition, the performance of the FeL4/H2O2 system was not influenced by anions and natural organics. This study verified the feasibility of modulating the catalytic performance of the complexes by changing the substituents and provided an efficient catalytic system for dyeing wastewater treatment.

ENHANCED DISEASE SUSCEPTIBILITY 1 promotes hydrogen peroxide scavenging to enhance rice thermotolerance.

Heat stress is a major factor limiting the production and geographic distribution of rice (Oryza sativa), and breeding rice varieties with tolerance to heat stress is of immense importance. Although extensive studies have revealed that reactive oxygen species (ROS) play a critical role in rice acclimation to heat stress, the molecular basis of rice controlling ROS homeostasis remains largely unclear. In this study, we discovered a novel heat-stress-responsive strategy that orchestrates ROS homeostasis centering on an immune activator, rice ENHANCED DISEASE SUSCEPTIBILITY 1 (OsEDS1). OsEDS1, which confers heat stress tolerance, promotes hydrogen peroxide (H2O2) scavenging by stimulating catalase activity through the OsEDS1-catalase association. The loss-of-function mutation in OsEDS1 causes increased sensitivity to heat stress, whereas the overexpression of OsEDS1 enhances thermotolerance. Furthermore, overexpression lines greatly improved rice tolerance to heat stress during the reproductive stage, which was associated with substantially increased seed setting, grain weight, and plant yield. Rice CATALASE C (OsCATC), whose activity is promoted by OsEDS1, degrades H2O2 to activate rice heat stress tolerance. Our findings greatly expand our understanding of heat stress responses in rice. We reveal a molecular framework that promotes heat tolerance through ROS homeostasis regulation, suggesting a theoretical basis and providing genetic resources for breeding heat-tolerant rice varieties.

Cysteine Sulfenylation of Protein Disulfide Isomerase Links Oxidative Stress to Thrombosis

Oxidative stress increases the risk of clinically significant thrombosis in the setting of inflammation, malignancy, infection, and dyslipidemia. Oxidants generated during oxidative stress are prothrombotic; however, the mechanisms by which oxidants induce thrombus formation is poorly understood. Protein disulfide isomerase (PDI) is a thiol isomerase that serves an important role in thrombus formation. It has a domain structure of a-b-b'-a', in which the aand a' domains are catalytic and the b and b' are substrate binding. A flexible x linker is between the b' and a'domains. PDI is uniquely sensitive to oxidative cysteine modification within the CGHC catalytic motif of its a and a'domains. Yet whether PDI cysteine modifications mediates thrombosis in an oxidative environment has not previously been studied. We hypothesized that oxidized PDI links oxidative stress to a prothrombotic phenotype through post-translational modification of proteins. We have previously shown that dyslipidemia promotes hydrogen peroxide generation from platelets and oxidizes proteins. Using hydrogen peroxide as a model oxidant, we found that oxidation of recombinant PDI promoted the loss of free thiols and inhibited reductase activity in a dose-dependent manner (IC50= 3.3 ± 0.12 µM). To understand how free thiols were lost, we used a benzothiazine-based nucleophilic probe, termed BTD, to label sulfenic acid. The transient cysteine sulfenic acid (S-OH) was detected by BTD labeling in wildtype PDI following exposure to hydrogen peroxide, but not in a PDI mutant in which all active site cysteines had been mutated to alanine. PDI exposure to oxidized lipoprotein particles (OxLDL) or 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, also promoted its sulfenylation. Using single cysteine mutants of PDI to identify the sulfenylation site, we found that Cys56 was preferentially sulfenylated as mutation of this cysteine prevented further labeling of the sulfenic acid probe. To assess whether interdomain interactions influenced sulfenylation, we evaluated BTD labeling in isolated fragments of PDI. Sulfenylation was identified in the a domain, consistent with Cys56 labeling, and was significantly enhanced in the ab fragment, implicating an interaction between the a and b domains in sulfenylation. No labeling was observed in an isolated b'xa' fragment. Further analysis of structural elements revealed that a conserved Arg120 within the a domain regulates Cys56 reactivity. Indeed, mutation of Arg120 to Ala prevented sulfenylation by peroxides compared to the wildtype control. Maleimide labeling showed that sulfenylated PDI is an intermediary that resolves into disulfided PDI. To determine whether this disulfided PDI promotes oxidase activity, we used a denatured and reduced RNAse that refolds when disulfides are transferred from oxidized PDI to the RNAse. PDI oxidized by hydrogen peroxide promoted RNAse refolding, whereas reduced PDI did not. A selective inhibitor of sulfenylation, arsenite, prevented RNAse refolding, indicating that hydrogen peroxide-induced oxidation of PDI proceeds through a sulfenic acid intermediate. Since PDI is secreted from cells, we evaluated whether activated cells release sulfenylated PDI using both human vein endothelial cells (HUVECs) and platelets. Sulfenylated PDI was increased in the cultured media of HUVECs stimulated with thrombin and in the releasate of platelets stimulated via PAR1 or glycoprotein VI. OxLDL exposure sensitizes platelets to activation by low doses of agonists. Inhibition of PDI using a neutralizing antibody inhibited augmentation of platelet aggregation by oxLDL, suggesting that oxidation of PDI by oxLDL promotes platelet activation. The ability of oxLDL to enhance the prothrombotic effect of PDI was tested in vivo in a murine model of laser-induced thrombus formation. Mice were infused with either control IgG or IgG directed at PDI, followed by the infusion of oxLDL. OxLDL significantly enhanced thrombus formation in this model. The effect of oxLDL was inhibited by anti-PDI IgG but not control IgG antibody or buffer, implicating PDI as an effector of oxLDL-augmented thrombus formation. In conclusion, our study demonstrates sulfenylation of PDI and shows that PDI sulfenylation retains PDI oxidase activity. Oxidation of PDI by oxidants such as oxLDL occurs in platelets and in endothelium and promotes thrombosis in the setting of oxidative stress.

Confined Gold Single Atoms-MXene Heterostructure-Based Electrochemiluminescence Functional Material and Its Sensing Application.

Herein, based on electronic metal-support interaction (EMSI), a gold single atom confined MXene (AuSA/MXene) heterostructure was developed as the highly efficient electrochemiluminescence (ECL) functional material, which greatly improved the electrochemical properties and broadened the sensing application of MXenes. Gold single atoms were confined into the vacancy defects of Ti3C2Tx MXene, which could effectively avoid the masking of catalytic active sites. Meanwhile, electron transport could be accelerated with the assistance of titanium dioxide on the MXene nanosheets. Therefore, the AuSA/MXene heterostructure had high catalytic activity and electrical activity to promote hydrogen peroxide to generate free radicals, which achieved high-efficiency ECL. Eventually, the AuSA/MXene heterostructure was used to construct a Faraday cage-type ECL sensor with fluid nanoislands to detect miRNA-187 in triple-negative breast cancer tumor tissues.

Strong Pyro-Electro-Chemical Coupling of Elbaite/H2O2 System for Pyrocatalysis Dye Wastewater

Elbaite is a natural silicate mineral with a spontaneous electric field. In the current study, it was selected as a pyroelectric catalyst to promote hydrogen peroxide (H2O2) for dye decomposition due to its pyro-electro-chemical coupling. The behaviors and efficiency of the elbaite/H2O2 system in rhodamine B (RhB) degradation were systematically investigated. The results indicate that the optimal effective degradability of RhB reaches 100.0% at 4.0 g/L elbaite, 7.0 mL/L H2O2, and pH = 2.0 in the elbaite/H2O2 system. The elbaite/H2O2 system exhibits high recyclability and stability after recycling three times, reaching 94.5% of the degradation rate. The mechanisms of RhB degradation clarified that the hydroxyl radical (·OH) is the main active specie involved in catalytic degradation in the elbaite/H2O2 system. Moreover, not only does elbaite act as a pyroelectric catalyst to activate H2O2 in order to generate the primary ·OH for subsequent advanced oxidation reactions, but it also has the role of a dye sorbent. The elbaite/H2O2 system shows excellent application potential for the degradation of RhB.

CD36 Activation Enhances Hydrogen Peroxide Generation in Human Platelets

Cardiovascular disease remains the leading cause of death in the United States and thrombosis following atherosclerotic plaque rupture represents a significant portion of this mortality. Our lab and others have previously shown that oxidized lipids in low density lipoprotein (LDL) particles (oxLDL) serve as a “danger” signal that is recognized by CD36, a scavenger receptor of the innate immune system, found on platelets, and other vascular cells, that promotes platelet hyper-reactivity and thrombogenesis. Recently published data from our lab suggests that oxLDL-CD36 signaling in platelets involves generation of reactive oxygen species (ROS) that are important signaling pathway regulators and contribute to the sustained activation of the redox-sensitive MAPK, ERK5. This pathway is an important contributor to platelet activation and thrombosis. It is not well understood how CD36-dependent ROS generation maintains platelets under hyperlipidemic conditions in a “hypersensitive” state. Our hypothesis is that oxLDL acting through CD36 stimulates specific hydroperoxide species to modulate platelet signaling pathways. Using reverse-phase HPLC to detect 7-hydroxycoumarin (COH), the stable fluorescent product of the reaction between hydroperoxides and coumarin boronic acid (CBA), we selectively measured intracellular hydroperoxide generation in washed human platelets. Platelets showed a dose-dependent increase in COH accumulation of 70 ± 20%, 81 ± 13%, and 84 ± 16% after stimulation with oxLDL 25 μg/mL, 50 μg/mL, or 100 μg/mL, respectively (p=0.0115, p<0.01, p<0.01). Equivalent doses of native LDL produced no significant increase in COH accumulation. Platelets also showed a time-dependent increase in COH with maximal accumulation after 60 minutes of 50 μg/mL oxLDL stimulation (p<0.001). Previously published functional aggregometry data suggested that PEG-catalase, an enzyme that promotes hydrogen peroxide (H2O2) breakdown, prevents oxLDL-stimulated platelet activation and aggregation. Here we showed that pre-treatment of platelets with PEG-catalase blunted oxLDL-stimulated COH accumulation by 42 ± 8.6% (p=0.0106). In addition to H2O2, CBA reacts with peroxynitrite, but inhibition of platelet nitric oxide synthase with L-NG-Nitroarginine methyl ester (L-NAME) did not alter COH generation after oxLDL treatment when compared to oxLDL alone. Since CD36 signaling activates platelets through “non-classical” pathways, we examined how classic platelet agonists affected oxLDL-stimulated hydroperoxide generation. Treatment with collagen-related peptide (CRP) showed no significant increase in COH accumulation, but co-stimulation with oxLDL and CRP showed a 185 ± 26.4% increase in COH accumulation, as compared to oxLDL alone (p<0.0001), suggesting a synergistic effect between the oxLDL-CD36 and collagen-GPVI signaling pathways. This effect was not observed after thrombin or ADP treatment. Further studies are necessary to elucidate how oxLDL-stimulated hydroperoxide generation affects platelet signaling. Taken together our data suggests that oxLDL specifically generates H2O2 in platelets to promote a hyper-sensitive state and collagen-GPVI signaling may enhance this effect promoting thrombosis in pro-atherogenic conditions. Since mice and humans lacking CD36 do not demonstrate a bleeding diathesis and form normal thrombi, we reason that targeting CD36-mediated redox mechanisms has clinical potential to reduce the risk of atherothrombosis without compromising normal physiological hemostasis responses, unlike current anti-platelet agents in clinical use. DisclosuresNo relevant conflicts of interest to declare.

Exogenous pipecolic acid modulates plant defence responses against Podosphaera xanthii and Pseudomonas syringae pv. lachrymans in cucumber (Cucumis sativus L.).

Systemic acquired resistance (SAR) is a long-lasting and broad-based resistance that can be activated following infection with (a)virulent pathogens and treatment with exogenous elicitors. Pipecolic acid (Pip), a Lys-derived non-protein amino acid, naturally occurs in many different plant species, and its N-hydroxylated derivative, N-hydroxypipecolic acid (NHP), acts as a crucial regulator of SAR. In the present study, we conducted a systemic analysis of the defence responses of a series of D,L-Pip-pretreated Cucumis sativus L. against Podosphaera xanthii (P. xanthii) and Pseudomonas syringae pv. lachrymans (Psl). The effects of D,L-Pip on ROS metabolism, defence-related gene expression, SA accumulation and activity of defence-related enzymes were evaluated. We show that exogenously applied D,L-Pip successfully induces SAR in cucumber against P. xanthii and Psl, but not Fusarium oxysporum f. sp. cucumerinum (Foc). Exogenous application of D,L-Pip via the root system is sufficient to activate the accumulation of free and conjugated salicylic acid (SA), and earlier and stronger upregulation of SAR-associated gene transcription upon P. xanthii infection. Furthermore, D,L-Pip treatment and subsequent pathogen inoculation promote hydrogen peroxide and superoxide accumulation, as well as Rboh transcription activation in cucumber plants, suggesting that D,L-Pip-triggered ROS production might be involved in enhanced defence reactions against P. xanthii. We also demonstrate that D,L-Pip pretreatment increases the activity of defence-associated enzymes, including peroxidase, chitinase and β-1,3-glucanase. The results presented in this report provide promising features of Pip as an elicitor in cucumber and call for further studies that may uncover its potential in production areas against different phytopathogens.

Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia

AbstractArterial thrombosis in the setting of dyslipidemia promotes clinically significant events, including myocardial infarction and stroke. Oxidized lipids in low-density lipoproteins (oxLDL) are a risk factor for athero-thrombosis and are recognized by platelet scavenger receptor CD36. oxLDL binding to CD36 promotes platelet activation and thrombosis by promoting generation of reactive oxygen species. The downstream signaling events initiated by reactive oxygen species in this setting are poorly understood. In this study, we report that CD36 signaling promotes hydrogen peroxide flux in platelets. Using carbon nucleophiles that selectively and covalently modify cysteine sulfenic acids, we found that hydrogen peroxide generated through CD36 signaling promotes cysteine sulfenylation of platelet proteins. Specifically, cysteines were sulfenylated on Src family kinases, which are signaling transducers that are recruited to CD36 upon recognition of its ligands. Cysteine sulfenylation promoted activation of Src family kinases and was prevented by using a blocking antibody to CD36 or by enzymatic degradation of hydrogen peroxide. CD36-mediated platelet aggregation and procoagulant phosphatidylserine externalization were inhibited in a concentration-dependent manner by a panel of sulfenic acid–selective carbon nucleophiles. At the same concentrations, these probes did not inhibit platelet aggregation induced by the purinergic receptor agonist adenosine diphosphate or the collagen receptor glycoprotein VI agonist collagen-related peptide. Selective modification of cysteine sulfenylation in vivo with a benzothiazine-based nucleophile rescued the enhanced arterial thrombosis seen in dyslipidemic mice back to control levels. These findings suggest that CD36 signaling generates hydrogen peroxide to oxidize cysteines within platelet proteins, including Src family kinases, and lowers the threshold for platelet activation in dyslipidemia.

Graphitic N in nitrogen-Doped carbon promotes hydrogen peroxide synthesis from electrocatalytic oxygen reduction

Electrocatalytic two-electron oxygen reduction reaction (2e− ORR) is a promising strategy to achieve hydrogen peroxide (H2O2) production, which can replace the anthraquinone method in industrial processes. Nitrogen-doped carbon materials are active and selective electrocatalysts for 2e− ORR; however, it remains challenging to develop N-doped carbons for practical H2O2 production and pinpoint the exact role of nitrogen functionalities. Here, we examine covalent organic framework-derived nitrogen-doped carbons with well-defined porous structure and tunable N species for electrocatalytic H2O2 production. Electrochemical studies show their highest ORR activity and H2O2 selectivity of up to 75% in alkaline electrolyte. Notably, chronoamperometric bulk electrolysis achieves an unprecedented carbon-catalyzed H2O2 yield rate of 1286.9 mmol gcatalyst−1 h−1 and a faradaic efficiency of 69.8% at pH 13. X-ray photoelectron spectroscopy analysis combined with control experiments reveals that graphitic N is responsible for H2O2 production from 2e− ORR on N-doped carbons. Our work provides insights into the rational development of heteroatom-doped carbon electrocatalysts for efficient H2O2 generation.

IL-4 and IL-17A Cooperatively Promote Hydrogen Peroxide Production, Oxidative DNA Damage, and Upregulation of Dual Oxidase 2 in Human Colon and Pancreatic Cancer Cells.

Dual oxidase 2 (DUOX2) generates H2O2 that plays a critical role in both host defense and chronic inflammation. Previously, we demonstrated that the proinflammatory mediators IFN-γ and LPS enhance expression of DUOX2 and its maturation factor DUOXA2 through STAT1- and NF-κB‒mediated signaling in human pancreatic cancer cells. Using a panel of colon and pancreatic cancer cell lines, we now report the induction of DUOX2/DUOXA2 mRNA and protein expression by the TH2 cytokine IL-4. IL-4 activated STAT6 signaling that, when silenced, significantly decreased induction of DUOX2. Furthermore, the TH17 cytokine IL-17A combined synergistically with IL-4 to increase DUOX2 expression in both colon and pancreatic cancer cells mediated, at least in part, by signaling through NF-κB. The upregulation of DUOX2 was associated with a significant increase in the production of extracellular H2O2 and DNA damage-as indicated by the accumulation of 8-oxo-dG and γH2AX-which was suppressed by the NADPH oxidase inhibitor diphenylene iodonium and a DUOX2-specific small interfering RNA. The clinical relevance of these experiments is suggested by immunohistochemical, microarray, and quantitative RT-PCR studies of human colon and pancreatic tumors demonstrating significantly higher DUOX2, IL-4R, and IL-17RA expression in tumors than in adjacent normal tissues; in pancreatic adenocarcinoma, increased DUOX2 expression is adversely associated with overall patient survival. These data suggest a functional association between DUOX2-mediated H2O2 production and induced DNA damage in gastrointestinal malignancies.

Surface engineering at the interface of core/shell nanoparticles promotes hydrogen peroxide generation

Hydrogen peroxide (H2O2), an environmentally friendly oxidant, has already been widely used in many chemical synthesis and industrials as an alternative to replace traditional oxidants including chlorinated oxidizers and strong acids. However, the conventional synthesis method confronts intense energy cost, tedious separation procedures and high cost, which is not competitive with traditional oxidants. Although direct H2O2 synthesis from H2 and O2 is a green and atomically economic reaction, satisfactory activity and desirable selectivity still remain formidable challenges. Herein, for the first time, a class of Pd@NiO-x nanoparticles (NPs) (x = 1, 2, 3 and 4) with a unique core@shell interface structure has been created to achieve high activity, selectivity and stability for the direct H2O2 synthesis. A precise thermal annealing on Pd@Ni-x NPs revealed that the resulting Pd@NiO-x NPs exhibited the volcano-like activity toward direct H2O2 synthesis as a function of annealing temperature and time. By tuning the composition of Pd@NiO-x NPs and the reaction condition, the efficiency of H2O2 synthesis could be well optimized with 5 wt% Pd@NiO-3/TiO2 exhibiting the highest productivity (89 mol/(kgcat h)) and selectivity (91%) to H2O2 as well as excellent stability, making it one of the best catalysts for direct H2O2 synthesis reported to date.

New evidence of the effect of the chemical structure of activated carbon on the activity to promote radical generation in an advanced oxidation process using hydrogen peroxide

The influence of seven commercial activated carbons (ACs) to promote hydrogen peroxide decomposition and radical generation is assessed during four operating cycles. The amount of generated hydroxyl radicals is estimated from quenching experiments using methanol as a radical scavenger. The change in chemical surface composition of ACs upon contact with hydrogen peroxide after each operating cycle is measured by Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and by following the change in the value of the pH of the point of zero charge (pHPZC). Results reveal that when ACs are exposed to hydrogen peroxide for extended periods, their chemical surface composition is modified, reducing the capacity of these materials to promote hydrogen peroxide decomposition, and in turn decreasing the generation of hydroxyl radicals. Moreover, DRIFTS analyses show that ACs with an appreciable content of basic surface functionalities, such as chromene-type structures, would guarantee a continuous radical generation, reducing the loss of catalytic activity.

Laccase-13 Regulates Seed Setting Rate by Affecting Hydrogen Peroxide Dynamics and Mitochondrial Integrity in Rice.

Seed setting rate is one of the most important components of rice grain yield. To date, only several genes regulating setting rate have been identified in plant. In this study, we showed that laccase-13 (OsLAC13), a member of laccase family genes which are known for their roles in modulating phenylpropanoid pathway and secondary lignification in cell wall, exerts a regulatory function in rice seed setting rate. OsLAC13 expressed in anthers and promotes hydrogen peroxide production both in vitro and in the filaments and anther connectives. Knock-out of OsLAC13 showed significantly increased seed setting rate, while overexpression of this gene exhibited induced mitochondrial damage and suppressed sugar transportation in anthers, which in turn affected seed setting rate. OsLAC13 also induced H2O2 production and mitochondrial damage in the root tip cells which caused the lethal phenotype. We also showed that high abundant of OsmiR397, the suppressor of OsLAC13 mRNA, increased the seed setting rate of rice plants, and restrains H2O2 accumulation in roots during oxidative stress. Our results suggested a novel regulatory role of OsLAC13 gene in regulating seed setting rate by affecting H2O2 dynamics and mitochondrial integrity in rice.

Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction

The 66-kDa Src homology 2 domain-containing protein (p66Shc) is a master regulator of reactive oxygen species (ROS). It is expressed in many tissues where it contributes to organ dysfunction by promoting oxidative stress. In the vasculature, p66Shc-induced ROS engenders endothelial dysfunction. Here we show that p66Shc is a direct target of the Sirtuin1 lysine deacetylase (Sirt1), and Sirt1-regulated acetylation of p66Shc governs its capacity to induce ROS. Using diabetes as an oxidative stimulus, we demonstrate that p66Shc is acetylated under high glucose conditions and is deacetylated by Sirt1 on lysine 81. High glucose-stimulated lysine acetylation of p66Shc facilitates its phosphorylation on serine 36 and translocation to the mitochondria, where it promotes hydrogen peroxide production. Endothelium-specific transgenic and global knockin mice expressing p66Shc that is not acetylatable on lysine 81 are protected from diabetic oxidative stress and vascular endothelial dysfunction. These findings show that p66Shc is a target of Sirt1, uncover a unique Sirt1-regulated lysine acetylation-dependent mechanism that governs the oxidative function of p66Shc, and demonstrate the importance of p66Shc lysine acetylation in vascular oxidative stress and diabetic vascular pathophysiology.

Core–shell structured, nano-Pd-embedded SiO2–Al2O3 catalyst (Pd@SiO2–Al2O3) for direct hydrogen peroxide synthesis from hydrogen and oxygen

In our previous studies, we proved that core/shell-structured Pd/SiO2 catalysts are more active for direct hydrogen peroxide synthesis than the conventional, impregnated Pd/SiO2 catalysts. In this study, the topic of our previous studies was extended to core/shell Pd/SiO2–Al2O3 catalysts, through which we examined the influence of acidic shell oxides (SiO2–Al2O3) on the hydrogen peroxide formation activity. The catalysts were prepared based on the Stöber method, and the reaction tests were performed by adding H3PO4 (0–0.03M) and in the presence of KBr (0.9mM). It was proved that the surface Brønsted acid sites promote hydrogen peroxide formation activity in a manner similar to protons dissolved in a reaction medium (ethanol–water). It was supposed that the influences of heterogeneous and homogeneous acids on catalytic activity are related to how much those acids promote the adsorption of Br− ions on the Pd surface. The highest H2O2 production rate was approximately 470mmol H2O2/gPdh, which was obtained using core/shell Pd/SiO2–Al2O3 catalysts under specific H3PO4 concentrations. This rate was higher than the highest value (∼ 420mmol H2O2/gPdh) achieved using core/shell Pd/SiO2 catalysts.

In This Issue

HomeCirculation ResearchVol. 115, No. 5In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published15 Aug 2014https://doi.org/10.1161/RES.0000000000000031Circulation Research. 2014;115:471Genome Editing of PCSK9 In Vivo (p 488)Download figureDownload PowerPointWith a single injection Ding et al reduce cholesterol levels in mice.High levels of low-density lipoprotein (LDL) in the blood are one of the primary risk factors for coronary heart disease, and even though statins can decrease LDL levels, their use does not completely mitigate the risk of heart disease. Moreover, some patients are intolerant of statin therapy. Hence, new strategies for reducing LDL levels are highly desirable. In humans, LDL levels are regulated by the liver enzyme PCSK9, and individuals with loss-of-function mutation in the PCSK9 gene are healthy but have lower LDL levels and a lower risk of coronary heart disease. Ding and colleagues therefore wondered whether mutating the Pcsk9 gene artificially in mice would mimic the benefits seen in human PCSK9 mutants. To mutate Pcsk9, the team performed gene-editing—a process whereby specially designed nucleases are directed to cut a particular DNA sequence of interest. They packaged a Pcsk9–specific nuclease into a liver-homing viral vector, and then injected it into mice. Four days after injection, they found that 50 percent of the liver cells contained the mutated protein. Importantly, the treated mice had lower levels of plasma PCSK9 enzyme and lower cholesterol levels. This proof-of-principle experiment paves the way for developing clinical-grade gene-editing strategies for targeting PCSK9 in humans.AMPK–ACC Signaling and Fatty Acid Oxidation (p 518)Download figureDownload PowerPointTheories of fatty acid metabolism in the heart require a rethink, say Zordoky et al.The kinase AMPK phosphorylates a variety of intracellular targets including the enzyme acetyl-CoA carboxylase (ACC), which is an inhibitor of fatty acid oxidation. AMPK phosphorylation of ACC inhibits the activity of this enzyme and thus AMPK indirectly promotes fatty acid metabolism. In the liver, inactivation of ACC by AMPK is essential for fat metabolism, but Zordoky and colleagues have now discovered that this is not the case in the heart. The team examined fatty acid metabolism in the hearts of genetically engineered mice expressing a version of ACC that was incapable of being phosphorylated by AMPK. They discovered that fatty acid oxidation was unaffected at both low and high workloads and even under ischemic conditions—known to specifically raise AMPK activity. These results indicate that while AMPK may be capable of promoting fatty acid metabolism in the heart it is certainly not required, and that other pathways must be involved. Discovering those pathways may be particularly relevant to the field of ischemia research, because fatty acid metabolism is thought to be the primary energy source in the heart during reperfusion.Ceramide Changes the Mediator of FID (p 525)Download figureDownload PowerPointCeramide promotes hydrogen peroxide production in the vessels of patients with coronary artery disease, report Freed et al.In response to shear stress, endothelial cells lining the blood vessels release factors that trigger vasodilation. In general, this flow-induced dilation (FID) is mediated by nitric oxide (NO), but in patients with coronary artery disease the endothelium switches from NO to hydrogen peroxide (H2O2) production. Both factors act as vasodilators, but while NO has anti-inflammatory, anti-thrombotic and anti-proliferative effects, H2O2 is pro-inflammatory, pro-thrombotic and pro-atherogenic. It is not clear why or how this switch occurs, but Freed and colleagues suspected that ceramide might be involved. Ceramide is not only is a risk factor for atherosclerosis, but it also promotes mitochondrial production of reactive oxygen species, such as H2O2. Hence, they incubated healthy human arterioles with ceramide and showed that FID switched from being NO-dependent to being H2O2-dependent. They also showed that in arterioles from patients with coronary artery disease, inhibiting ceramide synthesis led to the replacement of H2O2 production by NO production. Together these results suggest that ceramide is a pivotal regulator of damaging H2O2 production and that targeting ceramide or its associated pathways may be a novel therapeutic strategy for the treatment of coronary artery disease. Previous Back to top Next FiguresReferencesRelatedDetails August 15, 2014Vol 115, Issue 5 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000031 Originally publishedAugust 15, 2014 PDF download Advertisement

SO2 adsorption products on Pt nanoparticles as a function of electrode potential and oxidative properties of carrier gas: In situ sulfur K-edge XANES approach

In situ sulfur K-edge X-ray absorption near-edge structure spectroscopy is used to determine the nature of adsorbed SO2 species from a SO2/O2 gas mixture on carbon-supported Pt nanoparticles (Pt/VC). SO2 was adsorbed onto electrodes held at 0.1, 0.5, 0.7 and 0.9V vs. a reversible hydrogen electrode while flowing 1000ppm SO2 in O2 through the working electrode (WE) compartment. SO2 adsorption products from SO2/O2 are compared to those from SO2/N2 gas mixtures [Baturina, et al., Langmuir, 27 (2011) 14930]. The SO2 adsorption products are found to be essentially the same at electrodes held at 0.5, 0.7 and 0.9V. A major difference is observed at 0.1V, where (bi)sulfate ions are generated in the presence of SO2 in O2 likely due to a reaction between SO2 and H2O2 formed as a byproduct of the oxygen reduction reaction in the hydrogen adsorption region.(Bi)sulfate generation on Pt/VC catalysts held at 0.1V suggests that SO2 may act as a peroxide radical scavenger at the PEM fuel cell cathode. Although impurities such as SO2 and H2S usually promote hydrogen peroxide generation at the fuel cell cathodes, their detrimental effect may be diminished by their reaction with H2O2.