The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein

Altered redox balance is among the main contributing factors developing glioblastoma multiforme (GBM), a highly aggressive grade IV brain tumor. Neuropeptide substance P (SP) plays a key role in modifying the cellular redox environment by activating the neurokinin-1 receptor (NK1R). In this study, we aimed to investigate the redox-modulating properties of both SP and a commercially available NK1R antagonist, aprepitant in GBM cells. To detect the effect of aprepitant on the viability of U87 glioblastoma cells, resazurin assay was applied. The level of intracellular ROS was assessed using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. The expression of glutaredoxin, a well-known redox-active protein, was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Concurrently, the activity of glutaredoxin was also analyzed by a commercial kit (ZellBio GmbH). We found that SP increased the intracellular levels of reactive oxygen species (ROS) in U87 GBM cells, and aprepitant remarkably decreased this effect. We also explored the effects of SP/NK1R signaling on the glutaredoxin system as a major cellular redox buffer in GBM cells. SP reduced both expression and enzymatic activity of glutaredoxin, and these effects were significantly decreased by aprepitant. In conclusion, our results suggest a possible involvement of SP/NK1R signaling in GBM pathogenesis through oxidative stress and offering new insight for the application of aprepitant as a redox-modulating strategy in GBM patients.

The Redox Potential of the β-93-Cysteine Thiol Group in Human Hemoglobin Estimated from In Vitro Oxidant Challenge Experiments

Glutathionyl hemoglobin is a minor form of hemoglobin with intriguing properties. The measurement of the redox potential of its reactive β-93-Cysteine is useful to improve understanding of the response of erythrocytes to transient and chronic conditions of oxidative stress, where the level of glutathionyl hemoglobin is increased. An independent literature experiment describes the recovery of human erythrocytes exposed to an oxidant burst by measuring glutathione, glutathione disulfide and glutathionyl hemoglobin in a two-hour period. This article calculates a value for the redox potential E0 of the β-93-Cysteine, considering the erythrocyte as a closed system at equilibrium described by the Nernst equation and using the measurements of the literature experiment. The obtained value of E0 of −121 mV at pH 7.4 places hemoglobin as the most oxidizing thiol of the erythrocyte. By using as synthetic indicators of the concentrations the electrochemical potentials of the two main redox pairs in the erythrocytes, those of glutathione–glutathione disulfide and of glutathionyl–hemoglobin, the mechanism of the recovery phase can be hypothesized. Hemoglobin acts as the redox buffer that scavenges oxidized glutathione in the oxidative phase and releases it in the recovery phase, by acting as the substrate of the NAD(P)H-cofactored enzymes.

Oxidized sulfur-rich arc magmas formed porphyry Cu deposits by 1.88 Ga

Most known porphyry Cu deposits formed in the Phanerozoic and are exclusively associated with moderately oxidized, sulfur-rich, hydrous arc-related magmas derived from partial melting of the asthenospheric mantle metasomatized by slab-derived fluids. Yet, whether similar metallogenic processes also operated in the Precambrian remains obscure. Here we address the issue by investigating the origin, fO2, and S contents of calc-alkaline plutonic rocks associated with the Haib porphyry Cu deposit in the Paleoproterozoic Richtersveld Magmatic Arc (southern Namibia), an interpreted mature island-arc setting. We show that the ca. 1886–1881 Ma ore-forming magmas, originated from a mantle-dominated source with minor crustal contributions, were relatively oxidized (1‒2 log units above the fayalite-magnetite-quartz redox buffer) and sulfur-rich. These results indicate that moderately oxidized, sulfur-rich arc magma associated with porphyry Cu mineralization already existed in the late Paleoproterozoic, probably as a result of recycling of sulfate-rich seawater or sediments from the subducted oceanic lithosphere at that time.

Allicin, the Odor of Freshly Crushed Garlic: A Review of Recent Progress in Understanding Allicin’s Effects on Cells

The volatile organic sulfur compound allicin (diallyl thiosulfinate) is produced as a defense substance when garlic (Allium sativum) tissues are damaged, for example by the activities of pathogens or pests. Allicin gives crushed garlic its characteristic odor, is membrane permeable and readily taken up by exposed cells. It is a reactive thiol-trapping sulfur compound that S-thioallylates accessible cysteine residues in proteins and low molecular weight thiols including the cellular redox buffer glutathione (GSH) in eukaryotes and Gram-negative bacteria, as well as bacillithiol (BSH) in Gram-positive firmicutes. Allicin shows dose-dependent antimicrobial activity. At higher doses in eukaryotes allicin can induce apoptosis or necrosis, whereas lower, biocompatible amounts can modulate the activity of redox-sensitive proteins and affect cellular signaling. This review summarizes our current knowledge of how bacterial and eukaryotic cells are specifically affected by, and respond to, allicin.

Effect of Molybdenum on The Activity of Molybdoenzymes

The soil is a reservoir of various contaminants with heavy metals and has a strong cation exchange property. Among these heavy metals, molybdenum is an essential element that is required in small quantities for optimal plant growth and development. This useful heavy metal performs several biochemical and physiological tasks in plants and is also considered as an important component of various cellular enzymes and is actively involved in redox reactions. Mononuclear molybdenum-containing enzymes, as a rule, have a certain conserved metal center, coordinated by one or two pyranopterins. The pyranopterin fragment plays a key role in the properties of the metal site in the group of mononuclear enzymes of molybdenum with various functions: coordination; stabilization and modulation of the redox transitions of the center, acting as a redox buffer; and for redox regulation/compliance in a variety of catalytic reactions. The coordination sphere of the metal is equipped with oxygen and/or sulfur, selenium atoms in various forms. Tungsten is an antagonist of molybdenum and inhibits molybdoenzymes. In the current review we elaborately reviewed various studies regarding heavy metals - molybdenum and tungsten, their uptake mechanism, essential transporters, and also discuss about the destructive properties of heavy metals in response to their concentration.

Effects of the Incorporation of Tannin Extract from Quebracho Colorado Wood on Color Parameters, Lipid Oxidation, and Sensory Attributes of Beef Patties

The tannin extract of Quebracho Colorado wood (Schinopsis balansae and Schinopsis lorentzii) is rich in proanthocyanidins with demonstrated powerful scavenging activity against free radicals. Currently, this extract is used in the wine industry to improve sensory attributes, stabilize color, and act as a redox buffer. In this study, we hypothesized that condensed tannins from Quebracho Colorado wood could be incorporated into beef patties as a natural antioxidant source to improve shelf life. Patties formulated with tannin extract (0, 0.5%, 1%, and 1.5%) were evaluated for instrumental color, lipid oxidation, and sensory attributes. Patties were displayed under refrigerated aerobic conditions (PVC film) for 6 days for color and lipid oxidation analysis. For sensory analysis, patties were frozen immediately after formulation. Control (0%) samples were redder than samples formulated with 1.5% tannin during the first 4 days of display. For b*, samples formulated with 1.5% tannin were predominantly yellower during display. After day 4, chroma values were higher in samples formulated with 1.5% tannin. The inclusion of tannin extract improved lipid stability, however, levels above 0.5% decreased tenderness, softness, juiciness, and overall desirability of patties.