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Introduction: The post-translational oxidation of methionine to methionine sulfoxide is a reversible process, enabling repair of oxidative damage to proteins and the use of sulfoxidation as a regulatory switch. Methionine sulfoxide reductases catalyze the stereospecific reduction of methionine sulfoxide. One of the mammalian methionine sulfoxide reductases, MsrB3, has a signal sequence for entry into the endoplasmic reticulum (ER). In the ER, MsrB3 is expected to encounter a distinct redox environment compared to its paralogs in the cytosol, nucleus, and mitochondria. Aims: We sought to determine the location and arrangement of MsrB3 redox-active cysteines, which may couple MsrB3 activity to other redox events in the ER. Results: We determined the human MsrB3 structure using X-ray crystallography. The structure revealed that a disulfide bond near the protein amino terminus is distant in space from the active site. Nevertheless, biochemical assays showed that these amino-terminal cysteines are oxidized by the MsrB3 active site after its reaction with methionine sulfoxide. Innovation: This study reveals a mechanism to shuttle oxidizing equivalents from the primary MsrB3 active site toward the enzyme surface, where they would be available for further dithiol-disulfide exchange reactions. Conclusion: Conformational changes must occur during the MsrB3 catalytic cycle to transfer oxidizing equivalents from the active site to the amino-terminal redox-active disulfide. The accessibility of this exposed disulfide may help couple MsrB3 activity to other dithiol/disulfide redox events in the secretory pathway.

The unfolded protein response (UPR) maintains cellular proteostasis during stress by activating sensors located to the endoplasmic reticulum (ER) membrane. A major sensor for this response, ATF6α, is activated by release from ER retention and trafficking to the Golgi, where it is cleaved to generate a bZIP transactivator to initiate a transcriptional response. The reduction of a disulfide in monomeric ATF6α is thought to be necessary for release from retention, trafficking, and proteolysis. Here we show that, following ER stress, ATF6α undergoes a redox switch to form a disulfide bonded dimer, which traffics to the Golgi for cleavage by the S1P protease. Additionally, we find that overexpression of ERp18 attenuates dimer formation thereby limiting Golgi trafficking. Our results provide mechanistic insight into activation of the ATF6α pathway, revealing an unexpected role for redox-dependent oligomerization prior to Golgi trafficking.

Floor water inrush has always been an important problem affecting coal mine safety. The water inrush from the deep coal seam floor is the final manifestation of the water inrush channel formed by the expansion and penetration of rock mass cracks under the combined action of a high ground temperature, high ground stress, high karst water pressure and strong mining disturbance. The fault is a structurally weak plane developed in the complete rock layer, which can be regarded as a permeable channel with good permeability. In order to explore the location of confined water from the fault to rock stratum caused by the tensile fracture of a fault during floor water inrush, floor water inrush is regarded as the result of the joint action of water pressure and mining stress. The COMSOL Multiphysics numerical simulation software was used to simulate the advancing process of the working face of the coal seam with a fault structure. Different fault dip models were established for comparative analysis. The objective weight CRITIC based on data volatility was used to analyze the water pressure and principal stress near the fault. The results show that the uplift strength of highly confined water increases with the increase in the fault dip angle, and the weight of water pressure near the fault has a certain relationship with the location of the water body entering the rock stratum from the fault.

Aims This study aimed to examine the effect of a 12-week vitamin D supplementation and exercise training alone and in combination on glycemic control and bone health in Chinese type 2 diabetes patients.MethodsSixty-one type 2 diabetes patients (age, 33–65 years; 72.0% men) with non-insulin dependence were randomized into the 12-week vitamin D group (1000 IU/day), exercise group (60%–80% of maximal heart rate, 1 h/time, 2–3 times/week), vitamin D combined with exercise group, and control group. A 75-g oral glucose tolerance test was used to estimate glycemic control. Dual X-ray absorptiometry was used to examine bone health (bone mass content and bone mass density) and body fat percentage (%).Results During the 75-g oral glucose tolerance test, lower glucose and higher insulin levels were found in the vitamin D combined with exercise group, vitamin D group, and exercise group after intervention than before intervention, although the differences were not statistically significant. A significant exercise and vitamin D interaction for the insulinogenic index (P = 0.032) and a borderline interaction for the glucose disposition index (P = 0.051) were observed, while no further independent effect was observed. Compared with non-vitamin D supplementation, vitamin D supplementation significantly alleviated the loss of total bone mass content (95% CI: -29.9–19.4 vs. -74.9–-24.7), trunk bone mass content (95% CI: -24.1–19.5 vs. -56.1–-11.7), and spine bone mass density (95% CI: -0.03–0.03 vs. -0.07–-0.01).ConclusionsThe findings suggest that 12-week combined vitamin D and exercise intervention has a potentially positive effect on glycemic control, and vitamin D supplementation plays an important role in the prevention of bone loss, which was identified in the exercise alone group. Further studies are needed to elucidate the long-term effect of combined vitamin D and exercise intervention in type 2 diabetes patients.The study was registered in the Chinese Clinical Trial System (No. ChiCTR1800015383).

Vehicular ad hoc network (VANET) is a special form of Mobile Ad hoc Network (MANET), which plays a key role in the Intelligent Transportation System (ITS). Though many outstanding geographic routing protocols are designed for VANETs, Most of the existing proposals only consider a single factor, which makes the link easy to break. In this research, we propose a Routing Protocol Based on Multi-factor Decision (RMFD), which utilizes several features. The scheme is divided into two parts, namely vehicular decision management and intersection decision management. In the vehicular component, a route is establishes between two adjacent static nodes by calculating a fuzzy performance score using Triangular Fuzzy Number (TFN). In the Intersection management, static nodes located at the intersection are selects to decide which road segment the data will be forwarded to.

A new rare earth ternary iodate, Ce2I6O18, has been synthesized by a high temperature hydrothermal method with homemade alloy reactor equipment. It crystallizes in the monoclinic system space group P21 with a = 8.7252(2) A, b = 7.0474(1) A, c = 13.096(3) A, β = 90.81(0)°, Z = 2, and V = 805.2(3) A3. The material exhibits a three dimensional structure consisting of unlimited extending CeO9 polyhedrons and IO3 triangular pyramidal bilayers connected by I⋯O long bonds. The electronic band structure and optical properties of Ce2I6O18 were studied. It belongs to the type I phase-matchable class with an IR cutoff wavelength of 12.2 μm and second-harmonic generation (SHG) response of about 9 × KH2PO4 (KDP).

The membrane topology of vitamin K epoxide reductase (VKOR) is controversial with data supporting both a three transmembrane and a four transmembrane model. The positioning of the transmembrane domains and the loops between these domains is critical if we are to understand the mechanism of vitamin K oxidation and its recycling by members of the thioredoxin family of proteins and the mechanism of action of warfarin, an inhibitor of VKOR. Here we show that both mammalian VKOR isoforms adopt the same topology, with the large loop between transmembrane one and two facing the lumen of the endoplasmic reticulum (ER). We used a redox sensitive green fluorescent protein (GFP) fused to the N- or C-terminus to show that these regions face the cytosol, and introduction of glycosylation sites along with mixed disulfide formation with thioredoxin-like transmembrane protein (TMX) to demonstrate ER localization of the major loop. The topology is identical with the bacterial homologue from Synechococcus sp., for which the structure and mechanism of recycling has been characterized. Our results provide a resolution to the membrane topology controversy and support previous results suggesting a role for members of the ER protein disulfide isomerase (PDI) family in recycling VKOR.

Aqueous lithium ion batteries (ALIBs) attract wide attentions due to their high safety, low cost and environmental friendliness. The performance of anode material is the limiting step for the wide application of ALIBs. Here, a core-composite-shell structure of CuxTi2(PO4)3@Cu/C is rationally designed, synthesized and investigated as a promising anode material for ALIBs. With high electronic and lithium ion conductivity in internal core and external shell simultaneously, the CuxTi2(PO4)3@Cu/C anode material shows excellent electrochemical performance. It delivers a specific capacity 135 mA h·g−1 at 10 mA g−1 (the largest value reported), excellent rate behaviors of 95 mA h·g−1 at 2000 mA g−1, as well as long high rate cycling lifetimes (~80% after 900 cycles at 1000 mA g−1). This work not only provides a new anode material for ALIBs, but also proposes a new material structure design strategy and a facile synthesis method for the preparation of other alkali ions battery electrode materials.

Objective Irisin is a newly identified myokine, which is mainly secreted by skeleton muscle, adipose and cerebellar. It is shown to be related to some physiology process. The aim of this study is to evaluate the influence of exercise on circulating irisin concentrations in overweight or obese individuals Methods Searches were performed on nine online electronic databases including PubMed, EMbase, The Cochrane Library, web of science, Ebsco, CNKI, VIP, CBM and Wan-Fang Data databases. The search items were irisin, fibronectin type Ⅲ domain-containing protein 5, FNDC5, exercise, training, physical activity, obesity, overweight, obese, body mass index, BMI, adiposity and fat. Randomized controlled trials (RCT) or clinical controlled trials about the effect of exercise on circulating irisin concentrations in overweight or obese individuals in English or Chinese were eligible for the study. The trials compare exercise intervention with no intervention, or combined interventions of exercise and other with other intervention(s), and the exercise intervention is not one acute time. Besides, the trial objects belong to overweight or obese regardless of the judgement’s indicator. According to the criteria, the data extracted by two research independently. If there was disagreement, discussion between all the authors were used to settle. The risk of bias among the included studies was assessed by the Cochrane Collaboration Risk-of-Bias tool, which consists of seven domains and each one was judged to ‘unclear risk’ ‘low risk’, or ‘high risk’ following the recommendations detailed of the Cochrane handbook. Lastly an analysis about the final studies was done. Results The search identified a total of 855 possible articles. Of those, 364 were removed as duplicates, and the remaining 491 were screened for the titles and abstracts. The full-texts of 56 trials were retrieved to assess for eligibility. After the evaluation, four articles of RCTs were retained for the final system review from the year of 2015 to 2017, producing 6 study estimates. The assessments class of methods quantality of them are A. All the research subjects are more than 18 years old, and in one study subjects are men, men and women in two, women in three. The types of exercise intervention are dissimilar, such as strengthen or endurance exercise (including high intensity interval training, HIIT). In the duration of exercise, three studies are 8 weeks, and two for 12 weeks, one for 24 weeks. In circulating irisin, the detection methods of all is enzyme-linked immunosorbent assay, and three are in plasm, three in serum. Furthermore, the concentration unit in five studies is ng/ml, and one is µg/ml. Bonefate suggests that aerobic exercise with the frequency of 3 times per week for 24 week maintains plasma FNDC5/irisin of middle-age obese men, same as 8 weeks aerobic exercise for overweight/obese adults by Kim, but three is an opposite result from Wu, which proved that aerobic exercise of twelve weeks ascends serum irisin of young obese women. HIIT of eight or twelve weeks ascends serum irisin in sedentary obese women or young obese women according to Tofighi or Wu suggestion. Moreover, resistance exercise of 8 weeks significantly increases plasma irisin of overweight/obese adults From Kim’s study. Conclusions The study about effect of exercise on circulating irisin levels in overweight or obese individuals is not sufficient to come to a positive result, although the quality assessments of current evidences are high. Basing on the available literatures, exercise can maintain or improve circulating irisin levels in overweight or obese individuals. The effect needs to be illustrated by further RCTs with large sample size.

Vascular Nox (NADPH oxidase)-derived reactive oxygen species and endoplasmic reticulum (ER) stress have been implicated in hypertension. However, relationships between these processes are unclear. We hypothesized that Nox isoforms localize in a subcellular compartment-specific manner, contributing to oxidative and ER stress, which influence the oxidative proteome and vascular function in hypertension. Nox compartmentalization (cell fractionation), O 2 − (lucigenin), H 2 O 2 (amplex red), reversible protein oxidation (sulfenylation), irreversible protein oxidation (protein tyrosine phosphatase, peroxiredoxin oxidation), and ER stress (PERK [protein kinase RNA-like endoplasmic reticulum kinase], IRE1α [inositol-requiring enzyme 1], and phosphorylation/oxidation) were studied in spontaneously hypertensive rat (SHR) vascular smooth muscle cells (VSMCs). VSMC proliferation was measured by fluorescence-activated cell sorting, and vascular reactivity assessed in stroke-prone SHR arteries by myography. Noxs were downregulated by short interfering RNA and pharmacologically. In SHR, Noxs were localized in specific subcellular regions: Nox1 in plasma membrane and Nox4 in ER. In SHR, oxidative stress was associated with increased protein sulfenylation and hyperoxidation of protein tyrosine phosphatases and peroxiredoxins. Inhibition of Nox1 (NoxA1ds), Nox1/4 (GKT137831), and ER stress (4-phenylbutyric acid/tauroursodeoxycholic acid) normalized SHR vascular reactive oxygen species generation. GKT137831 reduced IRE1α sulfenylation and XBP1 (X-box binding protein 1) splicing in SHR. Increased VSMC proliferation in SHR was normalized by GKT137831, 4-phenylbutyric acid, and STF083010 (IRE1–XBP1 disruptor). Hypercontractility in the stroke-prone SHR was attenuated by 4-phenylbutyric acid. We demonstrate that protein hyperoxidation in hypertension is associated with oxidative and ER stress through upregulation of plasmalemmal-Nox1 and ER-Nox4. The IRE1–XBP1 pathway of the ER stress response is regulated by Nox4/reactive oxygen species and plays a role in the hyperproliferative VSMC phenotype in SHR. Our study highlights the importance of Nox subcellular compartmentalization and interplay between cytoplasmic reactive oxygen species and ER stress response, which contribute to the VSMC oxidative proteome and vascular dysfunction in hypertension.

The oxidation of methionine residues in proteins occurs during oxidative stress and can lead to an alteration in protein function. The enzyme methionine sulfoxide reductase (Msr) reverses this modification. Here, we characterise the mammalian enzyme Msr B3. There are two splice variants of this enzyme that differ only in their N-terminal signal sequence, which directs the protein to either the endoplasmic reticulum (ER) or mitochondria. We demonstrate here that the enzyme can complement a bacterial strain, which is dependent on methionine sulfoxide reduction for growth, that the purified recombinant protein is enzymatically active showing stereospecificity towards R-methionine sulfoxide, and identify the active site and two resolving cysteine residues. The enzyme is efficiently recycled by thioredoxin only in the presence of both resolving cysteine residues. These results show that for this isoform of Msrs, the reduction cycle most likely proceeds through a three-step process. This involves an initial sulfenylation of the active site thiol followed by the formation of an intrachain disulfide with a resolving thiol group and completed by the reduction of this disulfide by a thioredoxin-like protein to regenerate the active site thiol. Interestingly, the enzyme can also act as an oxidase catalysing the stereospecific formation of R-methionine sulfoxide. This result has important implications for the role of this enzyme in the reversible modification of ER and mitochondrial proteins.

In hypertension, activation of NADPH oxidases (Noxs) is associated with oxidative stress and vascular dysfunction. The exact role of each isoform in hypertension-associated vascular injury is still unclear. We investigated the compartmentalization of Noxs in VSMC from resistance arteries of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Expression of Nox1 and Nox4 was increased in SHR cells (96.6±28.7% and 48.2±21.2% vs WKY, p

Peroxiredoxins (Prxs) are a large and conserved family of peroxidases that are considered to be the primary cellular guardians against oxidative stress in all living organisms. Prxs share a thioredoxin fold and contain a highly-reactive peroxidatic cysteine in a specialised active-site environment that is able to reduce their peroxide substrates. The minimal functional unit for Prxs are either monomers or dimers, but many dimers assemble into decameric rings. Ring structures can further form a variety of high molecular weight complexes. Many eukaryotic Prxs contain a conserved GGLG and C-terminal YF motif that confer sensitivity to elevated levels of peroxide, leading to hyperoxidation and inactivation. Inactive forms of Prxs can be re-reduced by the enzyme sulfiredoxin, in an ATP-dependent reaction. Cycles of hyperoxidation and reactivation are considered to play an integral role in a variety of H

Novel graft copolymers, PTPA- g -PEAs containing poly(triphenylamine) (PTPA) backbone and poly(ethyl acrylate) (PEA) branches were synthesized by the oxidative coupling polymerization of triarylamine monomers followed by grafting of ethyl acrylate via an atom transfer radical polymerization (ATRP). Photorefractive (PR) composites based on the graft copolymers showed good static PR properties and fast response time under moderate conditions. The highest diffraction efficiency (19.7% at 45 V/μm) was observed with the composite containing the graft polymer with 18 mol% of graft density and 27 wt% of PTPA. And the fastest response (8 ms at 50 V/μm) was achieved when PTPA content was 68 wt%.

Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway.

Poly(4-butyltriarylamine)s with t-butyldimethylsilyl terminal protecting group (PBTPA-TBS) with various molecular weights were prepared by C-N coupling polymerization. The resulting precursors were postfunctionalized and subse- quently used as macroinitiators for atom transfer radial polymerization (ATRP) of n-butyl acrylate (n-BA) and ethyl acrylate (EA). Both the polymerization processes were controlled and the polymers were characterized by 1H NMR, gel permeation chromatography (GPC) and thermal properties, which confirmed the successful synthesis of all the poly-mers. The microphase separated behaviors of the poly (4-butyltriarylamine)-block-poly (butyl acrylate) (PBTPA-b-PBA) were examined by AFM in the film showing phase separation structures for all the polymers. The photorefractive property of the composite based on PBTPA-b-PBA block copolymer was evaluated by two-beam coupling experiment. A relative high gain coefficient of 42.7 cm?1 was obtained at the electric field of 31 V/?m.

The mitochondrial 2-Cys peroxiredoxin PrxIII serves as a thioredoxin-dependent peroxidase operating in tandem with its cognate partners, an organelle-specific thioredoxin (Trx2) and NADP-linked thioredoxin reductase (TRR2). This PrxIII pathway is emerging as a primary regulator of intracellular H(2)O(2) levels with dual roles in antioxidant defence and H(2)O(2)-mediated signalling. Here we describe the reconstitution of the mammalian PrxIII pathway in vitro from its purified recombinant components and investigate some of its overall properties. Employing the site-directed PrxIII mutants C47S, C66S and C168S, the putative N and C-terminal catalytic cysteine residues are shown to be essential for function whereas the C66S mutant retains full activity. The pathway attains maximal capacity at low H(2)O(2) concentrations (

Summary A crystal structure is reported for the C168S mutant of a typical 2-Cys peroxiredoxin III (Prx III) from bovine mitochondria at a resolution of 3.3 A. Prx III is present as a two-ring catenane comprising two interlocking dodecameric toroids that are assembled from basic dimeric units. Each ring has an external diameter of 150 A and encompasses a central cavity that is 70 A in width. The concatenated dodecamers are inclined at an angle of 55°, which provides a large contact surface between the rings. Dimer-dimer contacts involved in toroid formation are hydrophobic in nature, whereas the 12 areas of contact between interlocked rings arise from polar interactions. These two major modes of subunit interaction provide important insights into possible mechanisms of catenane formation.

A new bifunctional photorefractive active succinate (TPD-2DCVA) consisting of a tetraphenyldiaminobiphenyl (TPD) unit and 4-dicyanovinylaniline (DCVA) moieties was prepared, which forms stable mole...

NADPH oxidases (Noxs) are a major source of reactive oxygen species (ROS) in vascular cells. ROS are important signalling molecules with diverse actions. Mechanisms underlying differential ROS effects may relate, in part, to subcellular localization and Nox isoform specificity. We investigated the compartmentalization of Noxs and ROS in vascular smooth muscle cells (VSMC) and questioned whether these phenomena are altered in hypertension. VSMCs isolated from mesenteric arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studied. Subcellular compartmentalization of Noxs was evaluated by immunoblotting after organelle fractionation. ROS levels were measured by chemiluminescence (O2-) and amplex red (H2O2) in the absence or presence of of ML171 (Nox1 inhibitor), GKT136901 (Nox1/4 inhibitor), mito-tempol (mitochondrial-targeted antioxidant) and 4-PBA (ER stress inhibitor). Protein oxidation was assessed using the fluorescent probe DCP-Rho1 for protein sulfenylation and the oxyblot assay for protein carbonylation. Oxidation of protein tyrosine phosphatases (PTP) was evaluated by immunoblotting and Peroxiredoxin (Prx) oxidation was assessed by one-dimensional isoelectric focusing. Vascular reactivity was assessed by myography ± DTT (reducing agent) and peroxiredoxin inhibitor (Conoidin A). Expression of Nox1, Nox2 and Nox4 was greater in total cell homogenates from SHRSP versus WKY. Nox isoforms were detected in plasma membrane, ER and nucleus in both strains, but not in the mitochondria. Basal ROS generation was increased in SHRSP cells. In WKY only Nox1 inhibition decreased Ang II-induced ROS generation. Inhibition of Nox1 and Nox4 decreased basal and Ang II-induced ROS in SHRSP. Additionally, mito-tempol and 4-PBA reduced basal ROS generation in SHRSP. Analysis of protein oxidation revealed increased protein carbonylation and PTP oxidation in SHRSP. Furthermore, oxidation of the antioxidant enzymes Prxs was increased in SHRSP. Prx2, localised in the cytosol, and mitochondrial Prx3 were more oxidised in SHRSP cells than WKY cells. Noradrenaline-induced vascular contraction was reduced by DTT and Conoidin A. Our data demonstrate that Noxs are expressed in an organelle-specific manner, with Nox1,2,4 present in plasma membrane, ER and nucleus, but not in mitochondria. In SHRSP VSMCs Nox expression, ROS generation and protein oxidation are increased. Inhibition of oxidation attenuated vascular reactivity. These findings suggest an important role for Nox1/4 in oxidative stress and post-translational modification of proteins, processes that may play an important role in vascular dysfunction in hypertension.

Mitochondrial 2-cys peroxiredoxin III (PrxIII) is a key player in antioxidant defence reducing locally-generated H2O2 to H2O. A Phe to Leu (F190L) mutation in the C-terminal α-helix of PrxIII, mimicking that found in some bacteria and parasites, increases its resistance to hyperoxidation but has no obvious influence on peroxidase activity. Here we report on the oxidized and reduced crystal structures of bovine PrxIII F190L at 2.4 A and 2.2 A, respectively. Both structures exist as two-ring catenanes with their dodecameric rings inclined at 55o to each other, similar to that previously reported for PrxIII C168S. The new higher-resolution structures reveal details of the complex network of H-bonds stabilising the inter-toroid contacts. In addition, Arg123, the key conserved residue, that normally interacts with the catalytic cys (Cp, cys 47) is found in a distinct conformation extending away from the Cp while the characteristic Arg-Glu-Arg network, underpinning the active-site geometry also displays a distinctive arrangement, not observed previously. This novel active-site organisation may provide new insights into the dynamics of the large-scale conformational changes occurring between oxidized and reduced states.

Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2 that need to be regulated for H2O2 to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes to de novo disulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.

Background: Peroxiredoxin IV metabolizes endoplasmic reticulum-derived hydrogen peroxide. Results: In contrast to other peroxiredoxins, peroxiredoxin IV is insensitive to hyperoxidation within its cellular environment. Conclusion: There is a lack of a robust peroxiredoxin IV recycling system within the endoplasmic reticulum. Significance: Studying the reduction of peroxiredoxin IV highlights the different mechanisms for maintaining redox status within different cellular compartments., Typical 2-Cys peroxiredoxins are required to remove hydrogen peroxide from several different cellular compartments. Their activity can be regulated by hyperoxidation and consequent inactivation of the active-site peroxidatic cysteine. Here we developed a simple assay to quantify the hyperoxidation of peroxiredoxins. Hyperoxidation of peroxiredoxins can only occur efficiently in the presence of a recycling system, usually involving thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared with either the cytosolic or mitochondrial enzymes. Each enzyme is equally sensitive to hyperoxidation in the presence of a robust recycling system. Our results demonstrate that peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation.

The title compound is synthesized by hydrothermal reaction of Bi(NO3)3, HIO3, and HNO3 in H2O (pH ≈0.5, 215 °C, autoclave, 5 d; 75% yield).