NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation

© 2015 Elsevier Inc.All rights reserved. Laminar shear stress (LSS) triggers signals that ultimately result in atheroprotection and vasodilatation. Early responses are related to the activation of specific signaling cascades. We investigated the participation of redox-mediated modifications and in particular the role of hydrogen peroxide (H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular endothelial cells to short periods of LSS (12 dyn/cm2) resulted in the generation of superoxide radical anion as detected by the formation of 2-hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was corroborated by the increase in the fluorescence of the specific peroxide sensor HyPer. By using biotinylated dimedone we detected increased total protein sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4 (NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to identify the phosphatase SHP2 as a protein susceptible to sulfenylation under LSS. Given the dependence of FAK activity on SHP2 function, we explored the role of FAK under LSS conditions. FAK activation and subsequent endothelial NO synthase (eNOS) phosphorylation were promoted by LSS and both processes were dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4-null mice. These results support the idea that LSS elicits redox-sensitive signal transduction responses involving NOX4-dependent generation of hydrogen peroxide, SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation.Ministerio deEconomía y Competitividad, SAF2012-31338(S.L.),CSD2007-00020(S. L.), SAF2010-37926(J.V.); Instituto de Salud CarlosIII, REDinREN RD12/0021/0009(S.L.), ProteoRed-PT13/0001/0017(J.V.), RETIC-RD12/0042/0056(J.V.); Deutsche Forschungsgemeinschaft (SFB815/TP1toK.S.andR.P.B.andSCHR1241/1-1toK.S.); German Center for Cardiovascular Research; ComunidaddeMadrid “Fi-broteam” S2010/BMD-2321(S.L.);and Fundación Renal “Iñigo Alvarez deToledo” (S.L.). This work was also supported by European Cooperationin Science and Technology actionsBM-1203(EU-ROS) and BM-1005(ENOGAS) (S.L.).A.M.S.is supported by the British Heart Foundation.TheCBMSO receives institutional support from Fundación Ramón ArecesPeer Reviewe

Effect of sub-optimal moisture levels on the quality of groundnut (Arachis hypogaea L.) during storage in triple-layer hermetic storage bags

Storage is an important aspect of groundnut, as the in-shell and shelled kernels are prone to infestation by insects, pests, and fungi. Among several storage pests, the groundnut bruchid, Caryedon serratus, causes serious losses. Farmers often resort to different management practices, including hermetic storage, to control it. The moisture content of the commodity plays an important role in insect infestation during storage. Drying to safe moisture levels before storage is known to prevent the activity of various living organisms, such as storage pests. However, drying to low levels of moisture may not be economical for farmers, as they may not have access to devices to accurately check product moisture. In this regard, we wanted to demonstrate the efficacy of triple-layer hermetic storage bags in preventing the damage caused by C. serratus when the groundnuts are stored at intermediate (10%) and high (14%) levels of moisture compared to traditionally used bags such as polypropylene bags and jute bags. Groundnut pods at 10% moisture content and 14% moisture content were separately inoculated with adult bruchids and a toxigenic strain of Aspergillus flavus fungal inoculum before storing them for 6 months. Results from groundnut samples taken at two-month intervals indicated that groundnut pods stored in triple-layer hermetic bags were completely free from infestation by C. serratus by recording a zero number of eggs laid, number of pupae, adult emergence, percentage of loss, and percentage of damage up to 6 months of storage, by creating low oxygen (hypoxia) and high carbon dioxide (hypercarbia) conditions. Results also indicate no loss of pod weight stored in triple-layer bags, but a slight reduction in germination percentage was recorded due to a slight increase in fungal activity, but the reduction was significantly less in triple-layer plastic bags compared to other bag types. Similarly, biochemical constituents such as oil and protein content were slightly reduced in triple-layer plastic bags when pods were stored at a 10% moisture level, but a higher reduction was observed at a 14% moisture level. However, the reduction was very high and significant in other bag types at both 10 and 14% moisture levels

1-(2-Bromo-5-meth­oxy­phen­yl)-8-chloro-6-(2-fluoro­phen­yl)-4H-1,2,4-triazolo[4,3-a][1,4]benzodiazepine

The title compound, Csb 23Hsb 15BrClFNsb 4O, is an analogue of sedatives such as midazolam and alprazolam. Its geometrical parameters are normal and comparable with those of related compounds. The only possible significant inter-molecular inter-action is a C-H⋅sO bond

Anisotropic slip magneto-bioconvection flow from a rotating cone to a nanofluid with Stefan Blowing effects

A mathematical model for two dimensional steady laminar natural convective anisotropic slip boundary layer flows from a rotating vertical cone embedded in ethylene glycol bionanofluid is presented. The influence of Stefan blowing is also taken into account. Four different nonparticles namely Copper (Cu), Alumina (Al2O3), Copper Oxide (Cuo), Titanium Oxide (TiO2) are explored. Suitable similarity transformations are used to convert the governing equations into non-linear ordinary differential equations. These are then solved numerically, with appropriate boundary conditions, utilizing an implicit finite difference method (the BVP5C code in MATLAB). During computation Sc, Lb, Le and Lb are presented as unity, whilst Pr is taken as 151.The effects of the governing parameters on the dimensionless velocities, temperature, nanoparticle volume fraction, density of motile microorganisms as well as on the local skin friction, local Nusselt, Sherwood number and motile micro-organism number density are thoroughly examined via tables and graphs. It is found that the skin friction factor increases with tangential slip, magnetic field and Schmidt number whilst it decreases with blowing parameter and spin parameters. It is further observed that both the friction and heat transfer rates are highest for copper nanoparticles and lowest for TiO2 nanoparticles. Validation of the BVP5C numerical solutions with published results for several special cases of the general model is included. The study is relevant to electro-conductive bio-nano-materials processing

Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2a-mediated stress signaling

Source: doi: 10.15252/embj.201592394Phosphorylation of translation initiation factor 2α (eIF2α) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine–threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2α phosphorylation enhances cell survival. Here, we show that the reactive oxygen species‐generating NADPH oxidase‐4 (Nox4) is induced downstream of ATF4, binds to a PP1‐targeting subunit GADD34 at the endoplasmic reticulum, and inhibits PP1 activity to increase eIF2α phosphorylation and ATF4 levels. Other PP1 targets distant from the endoplasmic reticulum are unaffected, indicating a spatially confined inhibition of the phosphatase. PP1 inhibition involves metal center oxidation rather than the thiol oxidation that underlies redox inhibition of protein tyrosine phosphatases. We show that this Nox4‐regulated pathway robustly enhances cell survival and has a physiologic role in heart ischemia–reperfusion and acute kidney injury. This work uncovers a novel redox signaling pathway, involving Nox4–GADD34 interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains eIF2α phosphorylation to protect tissues under stress

NADPH oxidase signaling and cardiac myocyte function

The NADPH oxidase family of enzymes has emerged as a major source of reactive oxygen species (ROS) that is important in diverse cellular functions including anti-microbial defence, inflammation and redox signaling. Of the five known NADPH oxidase isoforms, several are expressed in cardiovascular cells where they are involved in physiological and pathological processes such as the regulation of vascular tone, cell growth, migration, proliferation, hypertrophy, apoptosis and matrix deposition. This article reviews current knowledge regarding the role of NADPH oxidases in cardiomyocyte function in health and disease

Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

British Heart Foundatio

4-amino-6-tert-butyl-3-thioxo-3,4-dihydro1,2,4-triazin-5(2H)-one

In the title compound, C\sb 7H\sb 12N\sb 4OS, the triazine ring is planar. The crystal structure is stabilized by inter\-molecular N—-H⋅sO hydrogen bonds which link the mol\-ecules into chains running along the \it c axis

2-Bromo-1-(4-methyl­phen­yl)-3-[4-(methyl­sulfan­yl)phen­yl]prop-2-en-1-one

The title compound, C17H15BrOS, crystallizes in a non-centrosymmetric space group and shows significant nonlinear optical activity