Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-Like Breast Carcinoma

AIMS: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

RESULTS: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression.

INNOVATION AND CONCLUSION: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma.

Caracterización electroquímica de la inserción de litio en MnNb2O6 (M= Mn, Co, Ni, Cu, Zn, Cd) y en Li3X2NbO6 (X= Mn, Co, Ni)

Tesis (Maestría en Ciencias con Especialidad en Ingeniería Cerámica) UANL

Rôle des microorganismes sur la spéciation du Cu, Zn et Al dans la rhizosphère de sols forestiers

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Superoxide dismutase functional regulation in neonatal hypoxia

Hypoxia is one of the major causes of damage to the fetal and neonatal brain and cardiac functions. in earlier studies we have reported the brain damage caused by hypoxia and resusciation with oxygen and epinephrine and have found that glucose treatment to hypoxic rats and hypoxic rats treated with oxygen shows a reversal of brain damage. during this study the findings may have clinical significance in the proper management of heart and brain functions.

Catalytic oxidation of cyclohexane over Cu-Zn-Cr ternary spinel systems

Spinel systems with the composition of Cu 1−x Zn x Cr 2 O 4 [x = 0 CCr, x = 0.25 CZCr-1, x = 0.5 CZCr-2, x = 0.75 CZCr-3 and x = 1 ZCr] were prepared by homogeneous co-precipitation method and were characterized by X-ray diffraction (XRD) and FT-IR spectroscopy. Elemental analysis was done by EDX, and surface area measurements by the BET method. The redox behavior of these catalysts in cyclohexane oxidation at 243 K using TBHP as oxidant was examined. Cyclohexanone was the major product over all catalysts with some cyclohexanol. 69.2% selectivity to cyclohexanol and cyclohexanone at 23% conversion of cyclohexane was realized over zinc chromite spinels in 10 h.

Hysteresis in a system driven by either generalized force or displacement variables: martensitic phase transition in single-crystalline Cu-Zn-Al

We report on experiments aimed at comparing the hysteretic response of a Cu-Zn-Al single crystal undergoing a martensitic transition under strain-driven and stress-driven conditions. Strain-driven experiments were performed using a conventional tensile machine while a special device was designed to perform stress-driven experiments. Significant differences in the hysteresis loops were found. The strain-driven curves show reentrant behavior yield point which is not observed in the stress-driven case. The dissipated energy in the stress-driven curves is larger than in the strain-driven ones. Results from recently proposed models qualitatively agree with experiments.

Germin is a manganese containing homohexamer with oxalate oxidase and superoxide dismutase activities

Germin is a hydrogen peroxide generating oxalate oxidase with extreme thermal stability; it is involved in the defense against biotic and abiotic stress in plants. The structure, determined at 1.6 A resolution, comprises beta-jellyroll monomers locked into a homohexamer (a trimer of dimers), with extensive surface burial accounting for its remarkable stability. The germin dimer is structurally equivalent to the monomer of the 7S seed storage proteins (vicilins), indicating evolution from a common ancestral protein. A single manganese ion is bound per germin monomer by ligands similar to those of manganese superoxide dismutase (MnSOD). Germin is also shown to have SOD activity and we propose that the defense against extracellular superoxide radicals is an important additional role for germin and related proteins.

Tryptophan oxidation by singlet molecular oxygen [O-2 ((1)Delta(g))]: Mechanistic studies using O-18-labeled hydroperoxides, mass spectrometry, and light emission measurements

Proteins have been considered important targets for reactive oxygen species. Indeed, tryptophan (W) has been shown to be a highly susceptible amino acid to many oxidizing agents, including singlet molecular oxygen [O-2 ((1)Delta(g))]. In this study, two cis- and trans-tryptophan hydroperoxide (WOOH) isomers were completely characterized by HPLC/mass spectrometry and NMR analyses as the major W-oxidation photoproducts. These photoproducts underwent thermal decay into the corresponding alcohols. Additionally, WOOHs were shown to decompose under heating or basification, leading to the formation of N-formylkynurenine (FMK). Using O-18-labeled hydroperoxides ((WOOH)-O-18-O-18), it was possible to confirm the formation of two oxygen-labeled FMK molecules derived from (WOOH)-O-18-O-18 decomposition. This result demonstrates that both oxygen atoms in FMK are derived from the hydroperoxide group. In addition, these reactions are chemiluminescent (CL), indicating a dioxetane cleavage pathway. This mechanism was confirmed since the CL spectrum of the WOOH decomposition matched the FMK fluorescence spectrum, unequivocally identifying FMK as the emitting species.

The late precambrian K-alkaline magmatism in the Ribeira Fold Belt: a case study of the Piracaia Pluton, State of São Paulo, SE Brazil, and its potential mineralization (Cu, Zn, Gd)

The Pluriserial Ribeira Magmatic System-590 of the Late Precambrian Ribeira Fold Belt comprises seven groups of high-K rocks of crustal or mantle origin with ages ranging between 620 and 570 Ma. One of these groups is represented by transalkaline suites akin to appinitic lamprophyres. The suites assemble one or more of following lithologies: (+/- quartz) gabbros and monzogabbros, (+/- quartz) diorites and monzodiorites, (+/- quartz) monzonites and syenites in addition to rare granites. All these rocks occur together in the Piracaia pluton, State of São Paulo. The mineralogy of the Piracaia suite comprises variable amounts of plagioclase (An 60-10), alkali-feldspars (orthoclase, microcline, albite), ortho- (Fe-hypersthene) and clinopyroxenes (augite), amphiboles (hornblende and rare late Fe-hastingsite), abundant biotite, quartz, opaques, sphene, allanite and zircon. Several magmatic pulses constructed the pluton. The Piracaia magma bulk trend evolved initially along the silica-undersaturation plane with simultaneous fractionation of accessory, mafic and felsic minerals. These are segregated in feldspar-rich cumulates. In the late stage, the evolutionary trend followed two distinct paths: one along the or-ab thermal barrier with the crystallization of syenites; the second one along the thermal valley in the or-ab-qz subsystem, producing quartz-syenites and granites. The source of the Piracaia magma was a 'vein-plus-wall-rock-system '. Together the pulses reflect increasing and decreasing participation of peridotites and mica pyroxenites, respectively, in the magmatogenic process. The magmatic pulses were stored in magma chambers, several drained by deep faults or fractures, which were successively reactivated and recharged. Each new pulse underwent mixing with earlier residual magma, followed by fractionation. During ascent through the hot and thickened post-collisional crust, the magma pulses underwent minor compositional changes by crustal contamination. The concentration of valuable elements (Cu, Zn, Gd) in the Piracaia pluton occurred during two phases of the magmatic evolution. Cu and Zn were enriched in cumulates and Gd was concentrated in residual quartz-syenitic veins. Due to their homogeneous dark colour and texture, the monzodiorites are exploited both for polished dimension stones and supports for sensitive scientific instruments. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Laüe back-reflection method for crystallographic orientation of a martensitic Cu-Zn-Al single crystal of the monoclinic system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Paper-based diffusive gradients in thin films technique coupled to energy dispersive X-ray fluorescence spectrometry for the determination of labile Mn, Co, Ni, Cu, Zn and Pb in river water

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adsorption of MX2 (M = Mn, Ni, Cu, Zn, and Cd; X = Cl, Br, and I) and FeCl3 by modified silica surface with imidazolylpropyl group

Silica gel surface modified with imidazolylpropyl group was used to adsorb MX2 (M = Mn, Ni, Cu, Zn, and Cd; X = Cl, Br, and I) and FeCl3 from ethanol and acetone solution. The adsorption capacity and the intensity of the adsorption were determined by using the Langmuir equation. The influences of the solvent, temperature, and degree of functionalization on the adsorption were also studied. The infrared spectra of the functionalized silica were recorded between 1700-1300 cm-1. The bands of the imidazole skeletal vibrations are shifted to higher frequencies upon metal-to-base nitrogen interaction. © 1985.

The characterization of a thermostable and cambialistic superoxide dismutase from thermus filiformis

The superoxide dismutase (TfSOD) gene from the extremely thermophilic bacterium Thermus filiformis was cloned and expressed at high levels in mesophilic host. The purified enzyme displayed approximately 25 kDa band in the SDS-PAGE, which was further confirmed as TfSOD by mass spectrometry. The TfSOD was characterized as a cambialistic enzyme once it had enzymatic activity with either manganese or iron as cofactor. TfSOD showed thermostability at 65, 70 and 80°C. The amount of enzyme required to inhibit 50% of pyrogallol autoxidation was 0·41, 0·56 and 13·73 mg at 65, 70 and 80°C, respectively. According to the circular dichroism (CD) spectra data, the secondary structure was progressively lost after increasing the temperature above 70°C. The 3-dimensional model of TfSOD with the predicted cofactor binding corroborated with functional and CD analysis. © 2013 The Society for Applied Microbiology.