268 research outputs found
Role of Superoxide Anions in the Redox Changes Affecting the Physiologically Occurring Cu(I)-Glutathione Complex
The physiologically occurring copper-glutathione complex, [Cu(I)-[GSH]2], has the ability to react continually with oxygen, generating superoxide anions (O2ââ). We addressed here the effects that superoxide removal has on the redox state of Cu(I) and GSH present in such complex and assessed the formation of Cu(II)-GSSG as a final oxidation product. In addition, we investigated the potential of a source of O2ââ
external to the Cu(I)-[GSH]2 complex to prevent its oxidation. Removal of O2ââ
from a Cu(I)-[GSH]2-containing solution, whether spontaneous or Tempol-induced, led to time-dependent losses in GSH that were greater than those affecting the metal. The losses in GSH were not accompanied by increments in GSSG but were largely accounted for by the cumulative formation of Cu(II)-GSSG molecules. Notably, the redox changes in Cu(I) and GSH were totally prevented when Cu(I)-[GSH]2 was coincubated with hypoxanthine/xanthine oxidase. Data suggest that the generation of O2ââ
by Cu(I)-[GSH]2 implies the obliged formation of an intermediate whose subsequent oxidation into Cu(II)-GSSG or back reduction into Cu(I)-[GSH]2 is favoured by either the removal or the addition of O2ââ, respectively
Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies
Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
Copper is a Cofactor of the Formylglycine-Generating Enzyme
Formylglycine-generating enzyme (FGE) is an O2 -utilizing oxidase that converts specific cysteine residues of client proteins to formylglycine. We show that CuI is an integral cofactor of this enzyme and binds with high affinity (KD =of 10-17 m) to a pair of active-site cysteines. These findings establish FGE as a novel type of copper enzyme
Transcriptional Alterations in Hereditary and Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors According to Genotype.
BACKGROUND
Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype. METHODS
Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed by real-time polymerase chain reaction analysis and immunohistochemistry. Gene expression profiles were analyzed by tumor genotype, and pathway analysis was curated. RESULTS
Consensus clustering of mRNA expression revealed separate clustering of NICs, VHL-associated NFPanNETs, and MEN1-associated NFPanNETs; whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs. Among many genes, platelet-derived growth factor receptor ÎČ (PDGFRB), lymphoid enhancer-binding factor-1 (Lef-1), cyclin-dependent kinase 4 (CDK4), and CDK6 were upregulated in VHL or MEN1 NFPanNETs, providing potential subtype-specific treatment targets. CONCLUSIONS
Distinct mRNA expression patterns were identified in sporadic-associated, VHL-associated, and MEN1-associated NFPanNETs. The current results uncover new pathways involved in NFPanNETs that are subtype-specific and provide potential new diagnostic or therapeutic targets based on tumor subtype. Cancer 2017. © 2017 American Cancer Society
DL-methionine supplementation of rice-and-bean diets affects gamma-glutamyltranspeptidase activity and glutathione content in livers of growing rats
Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties
Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to undergo oxidation. As a consequence, upon reaction with ROS, the antioxidant capacity of flavonoids is severely compromised. Other phenol-compromising reactions, such as those involved in the biotransformation of flavonoids, can also markedly affect their antioxidant properties. In recent years, however, increasing evidence has indicated that, at least for some flavonoids, the oxidation of such residues can in fact markedly enhance their original antioxidant properties. In such apparent paradoxical cases, the antioxidant activity arises from the pro-oxidant and/or electrophilic character of some of their oxidation-derived metabolites and is exerted by activating the Nrf2–Keap1 pathway, which upregulates the cell’s endogenous antioxidant capacity, and/or, by preventing the activation of the pro-oxidant and pro-inflammatory NF-κB pathway. This review focuses on the effects that the oxidative and/or non-oxidative modification of the phenolic groups of flavonoids may have on the ability of the resulting metabolites to promote direct and/or indirect antioxidant actions. Considering the case of a metabolite resulting from the oxidation of quercetin, we offer a comprehensive description of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties. An overlooked topic of great phytomedicine potential is thus unraveled
Antioxidant effect of 5-amino salicylic acid on copper-mediated LDL oxidation
The antioxidant effect of 5-Aminosalicylic acid (5-ASA) on copper-mediated LDL oxidation was followed either by the emitted chemiluminiscence (CL) or by UV-vis spectroscopy. 5-ASA addition extends the lag phase in a concentration-dependent manner without changes in the rate of the process in the autoaccelerated phase. The antioxidant behavior of 5-ASA was very similar to that of Trolox, a very efficient water soluble antioxidant. The copper-binding capacity of 5-ASA was evaluated by UV-visible spectroscopy. The addition of copper to a 5-ASA solution increases the absorbance at 332 nm and generates a new band at 298 nm. These changes in the UV-vis spectra indicate formation of a complex between 5-ASA and copper. However, LDL protection by 5-ASA is unrelated to its copper chelating capacit
Antioxidant Activity of Crude Extract, Alkaloid Fraction, and Flavonoid Fraction from Boldo (Peumus boldus Molina) Leaves
Identification of the transition state for fast reactions: The trapping of hydroxyl and methyl radicals by DMPO - A DFT approach
Up to date, attempts to locate the transition state (TS) for the trapping reaction between ÌOH and ÌDMPO have been unsuccessful, and the lack of molecular mechanisms by which ÌOH binds to the spin-trap constitutes a question still unsolved. Herein, we have taken a step forward on this task by describing the theoretical TS for the trapping of ÌOH and ÌCH 3 by DMPO and the intrinsic reaction coordinates. This work aims to provide new understandings on the molecular orbital (MO) interactions that rule these reaction paths. Besides we assessed the degree of involvement of weak interactions and the charge transfer (CT) phenomenon involved in such interactions. Regarding the trapping of ÌOH, the beginning of the reaction would be ruled by weak interactions to then give way to stronger MO interactions conducive to the formation of the TS. For ÌCH3, the reaction is, instead, early ruled by significant MO interactions, and a relatively small contribution in the weak interactions range. At the
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