Carlos Batthyany

Institut Pasteur de Montevideo | IP Montevideo · INDICyO

Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethe...

Motivation: There are several well-established paradigms for identifying and pinpointing discriminative peptides/proteins using shotgun proteomic data; examples are peptide-spectrum matching, de novo sequencing, open searches, and even hybrid approaches. Such an arsenal of complementary paradigms can provide deep data coverage, albeit some unident...

Chronic metabolic diseases, like obesity, type II diabetes and atherosclerosis often involve a low-grade and sterile systemic inflammatory state, in which activation of the pro-inflammatory transcription factor NF-kB and the NLRP3 inflammasome play a major role. It is well established that genetic inhibition of the NLRP3 inflammasome ameliorates ac...

Purpose: During sepsis and mechanical ventilation oxidative stress is generated by endothelial and inflammatory lung cells. Our main objective was to study pulmonary NO (nitric oxide) production and nitroxidative stress in mechanically-ventilated septic patients. Methods: We study 69 mechanically ventilated patients, 36 with sepsis and 33 withou...

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are for...

A system, method, computer readable medium and device for identifying discriminant spectrum clusters including receiving known input data set comprising spectra generated from biological samples known to either have or not have a biological condition where each spectrum may be either known to have been generated from the biological samples known to...

A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for bio...

Sirtuins are NAD⁺-dependent deacetylases reported as key factors in metabolism regulation, inflammation and stress response. Human sirtuin 6 (hSIRT6) is known as a histone 3 deacetylase despite of its low activity in vitro. Its deacetylase activity increases in the presence of fatty acids and possess long chain fatty acid deacylase activity. Studie...

Motivation: Around 75% of all mass spectra remain unidentified by widely adopted proteomic strategies. We present DiagnoProt, an integrated computational environment that can efficiently cluster millions of spectra and use machine learning to shortlist high-quality unidentified mass spectra that are discriminative of different biological conditions...

The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the h...

AgB purification from HF. A) Analysis by SDS-PAGE of the fractions obtained by anion exchange chromatography on Q-Sepharose of HF and subsequent ultracentrifugation in a KBr gradient (Figure is representative of analytical triplicates). Between 25 and 30 μg of each fraction were separated on a 15% polyacrylamide gel in reducing conditions (6 mM DTT...

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Characterisation of bovine AgB. bQSf proteins species were analysed by DGE followed by MALDI-TOF/TOF while the lipid moiety of bLdf was analysed by HPTLC. (PDF)

Echinococcus and host proteins identified in sQSf and bQSf by LC-MS/MS. (PDF)

Alignments of Echinococcus HLBPs named A0A068WMS7_EGHR and W6UNU2_ECHGR with their orthologous in Taenia solium and E. granulosus AgB subunits. (PDF)

Putative protein products of E. canadensis AgB2. Nucleotide sequence for AgB2 (ECANG7_10984) were obtained from E. canadensis genome available at http://parasite.wormbase.org. Putative products of ECANG7_10984 were predicted using the Expasy translate tool (http://web.expasy.org/cgi-bin/translate/dna_aa). (PDF)

Analysis of post-translational modifications: phosphorylation and formation of carbonyl groups in AgB subunits. (PDF)

Significant efforts are being made to minimize aflatoxin contamination in peanut seeds and one possible strategy is to understand and exploit the mechanisms of plant defense against fungal infection. In this study we have identified and characterized, at biochemical and molecular levels, plant protease inhibitors (PPIs) produced in peanut seeds of...

Cytochrome c is a small protein that functions as carrier in the mitochondrial respiratory chain and pro-apoptotic mediator in the cytosol. This protein can also act as a peroxidase when exposed to high doses of hydrogen peroxide; when interacting with cardiolipin, a phospholipid from the inner mitochondrial membrane or after its oxidative post-tra...

Significance: "Nitroproteomic" is under active development, as 3-nitrotyrosine in proteins constitutes a footprint left by the reactions of nitric oxide-derived oxidants that are usually associated to oxidative stress conditions. Moreover, protein tyrosine nitration can cause structural and functional changes, which may be of pathophysiological re...

Human Mn-containing superoxide dismutase (hMnSOD) is a mitochondrial enzyme that metabolizes superoxide radical (O2•-). O2•- reacts at diffusional rates with nitric oxide to yield a potent nitrating species, peroxynitrite anion (ONOO-). MnSOD is nitrated and inactivated in vivo, with active site Tyr34 as the key oxidatively-modified residue. We pre...

Bacteriophage J-1 was isolated in 1965 from an abnormal fermentation of Yakult using Lactobacillus casei strain Shirota, and a related phage, PL-1, was subsequently recovered from a strain resistant to J-1. Complete genome sequencing shows that J-1 and PL-1 are almost identical, but PL-1 has a deletion of 1.9 kbp relative to J-1, resulting in the l...

Peroxiredoxins (Prx) are efficient thiol-dependent peroxidases and key players in the mechanism of H2O2-induced redox signaling. Any structural change that could affect their redox state, oligomeric structure, and/or interaction with other proteins could have a significant impact on the cascade of signaling events. Several post-translational modifi...

Trypanosoma cruzi, the causative agent of Chagas disease, contains exclusively iron-dependent superoxide dismutases (Fe-SODs) located in different subcellular compartments. Peroxynitrite, a key cytotoxic and oxidizing effector biomolecule, reacted with T. cruzi mitochondrial (Fe-SODA) and cytosolic (Fe-SODB) SODs with second order rate constants of...

PknG from Mycobacterium tuberculosis is a Ser/Thr protein kinase that regulates key metabolic processes within the bacterial cell as well as signaling pathways from the infected host cell. This multi-domain protein has a conserved canonical kinase domain with N- and C-terminal flanking regions of unclear functional roles. The N-terminus harbors a r...

The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated l...

Context: Triosephosphate isomerase (TIM) is a ubiquitous enzyme that has been targeted for the discovery of small molecular weight compounds with potential use against Trypanosoma cruzi, the causative agent of Chagas disease. We have identified a new selective inhibitor chemotype of TIM from T. cruzi (TcTIM), 1,2,4-thiadiazol-5(4H)-one. Objective...

Antigen B (EgAgB) is the most abundant and immunogenic antigen produced by the larval stage (metacestode) of Echinococcus granulosus. It is a lipoprotein, the structure and function of which have not been completely elucidated. EgAgB apolipoprotein components have been well characterised; they share homology with a group of hydrophobic ligand bindi...

Infection by larval Echinococcus granulosus is usually characterized by tight inflammatory control. However, various degrees of chronic granulomatous inflammation are also observed, reaching a high point in infection of cattle by the most prevalent parasite strain worldwide, which is not well adapted to this host species. In this context, epithelio...

Adenosine triphosphate (ATP) is released by alveolar epithelial cells during ventilator-induced lung injury (VILI) and regulates fluid transport across epithelia. High CO(2) levels are observed in patients with "permissive hypercapnia," which inhibits alveolar fluid reabsorption (AFR) in alveolar epithelial cells. The authors set out to determine w...

Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed by reactions of nitric oxide and nitrite. NO2-FA exert anti-inflammatory signaling actions through post-translational protein modifications. We report that nitro-oleic acid (OA-NO2) stimulates proMMP-7 and proMMP-9 proteolytic activity via adduction of the conserved cysteine sw...

Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed by reactions of nitric oxide and nitrite. NO2-FA exert anti-inflammatory signaling actions through post-translational protein modifications. We report that nitro-oleic acid (OA-NO2) stimulates proMMP-7 and proMMP-9 proteolytic activity via adduction of the conserved cysteine sw...

The peroxisome proliferator-activated receptor-gamma (PPARgamma) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARgamma include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently, TZDs have raised concern after being linked with increased risk of peripheral edema, weight...

The peroxisome proliferator-activated receptor-γ (PPARγ) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARγ include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently TZDs have raised concern after being linked with increased risk of peripheral edema, weight gain, and ad...

Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability and endothelial dysfunction, with secondary oxidized and nitrated by-products of these reactions contributing to the pathogenesis of numerous vascular diseases. While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the vasculature, in stark contras...

Nitroalkene fatty acid derivatives manifest a strong electrophilic nature, are clinically detectable, and induce multiple transcriptionally regulated anti-inflammatory responses. At present, the characterization and quantification of endogenous electrophilic lipids are compromised by their Michael addition with protein and small-molecule nucleophil...

Xanthine oxidoreductase (XOR) generates proinflammatory oxidants and secondary nitrating species, with inhibition of XOR proving beneficial in a variety of disorders. Electrophilic nitrated fatty acid derivatives, such as nitro-oleic acid (OA-NO2), display anti-inflammatory effects with pleiotropic properties. Nitro-oleic acid inhibits XOR activity...

Nitroalkene derivatives of fatty acids act as adaptive, anti-inflammatory signalling mediators, based on their high-affinity PPARgamma (peroxisome-proliferator-activated receptor gamma) ligand activity and electrophilic reactivity with proteins, including transcription factors. Although free or esterified lipid nitroalkene derivatives have been det...

Posttranslational protein tyrosine oxidation, to yield 3-nitrotyrosine, is a biologically relevant protein modification related with acute and chronic inflammation and degenerative processes. It is usually associated with a decrease or loss in protein function. However, in some proteins, tyrosine nitration results in an increase or gain in protein...

Synthesis, physicochemical, and biological characterization of a series of alpha-tocopherol mimetics with NO-releasing capacity are reported. The selected NO-donor moieties were nitrooxy and furoxan. All products were tested for their in vitro NO-releasing capacities, vasoditating properties and mammal cytotoxic activities. The lipophilic-hydrophil...

Nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2) are present; however, their biological functions remain to be fully defined. Herein, we report that LNO2 and OA-NO2 inhibit lipopolysaccharide-induced secretion of proinflammatory cytokines in macrophages independent of nitric oxide formation, peroxisome proliferator-activated...

Nitric oxide ((*)NO)-derived reactive species nitrate unsaturated fatty acids, yielding nitroalkene derivatives, including the clinically abundant nitrated oleic and linoleic acids. The olefinic nitro group renders these derivatives electrophilic at the carbon beta to the nitro group, thus competent for Michael addition reactions with cysteine and...

Mass spectrometric analysis of human plasma and urine revealed abundant nitrated derivatives of all principal unsaturated fatty acids. Nitrated palmitoleic, oleic, linoleic, linolenic, arachidonic and eicosapentaenoic acids were detected in concert with their nitrohydroxy derivatives. Two nitroalkene derivatives of the most prevalent fatty acid, ol...

Synthesis and biological characterization of a series of alpha-tocopherol analogs with NO-releasing capacity are reported. The selected NO-donor moieties were nitrooxy and furoxan. All products were tested for their in vitro NO-releasing capacities, vasodilating properties, and antiplatelet activity. They were also capable of preventing LDL oxidati...

Low density lipoprotein (LDL) oxidation by peroxynitrite is a complex process, finely modulated by control of peroxynitrite formation, LDL availability and free-radical scavenging by nitric oxide (*NO), ascorbate and alpha-tocopherol (alpha -TOH). In the presence of CO2, lipid targets are spared at the expense of surface constituents. Since surface...

Cytochrome c-dependent electron transfer and apoptosome activation require protein-protein binding, which are mainly directed by conformational and specific electrostatic interactions. Cytochrome c contains four highly conserved tyrosine residues, one internal (Tyr67), one intermediate (Tyr48), and two more accessible to the solvent (Tyr74 and Tyr9...

The aqueous decay and concomitant release of nitric oxide (·NO) by nitrolinoleic acid (10-nitro-9,12-octadecadienoic acid and 12-nitro-9,12-octadecadienoic acid; LNO2) are reported. Mass spectrometric analysis of reaction products supports a modified Nef reaction as the mechanism accounting for the generation of ·NO by the aqueous reactions of fatt...

Nitric oxide (·NO) has been proposed to play a relevant role in modulating oxidative reactions in lipophilic media like biomembranes and lipoproteins. Two factors that will regulate ·NO reactivity in the lipid milieu are its diffusion and solubility, but there is no data concerning the actual diffusion (D) and partition coefficients (KP) of ·NO in...

Decreased diaphragmatic contractility and organ failure observed during sepsis is mediated by an overproduction of nitric oxide ((.)NO)-derived species, mitochondria being a major target of oxidative and nitrative stress. We tested the potential protective effects of (a) a novel synthetic antioxidant, the manganese(III) 5,10,15,20-tetrakis(N-ethylp...

Peroxynitrite is a powerful oxidant implicated as a mediator in nitric oxide ((*)NO)- and superoxide (O(2)(*)(-))-dependent toxicity. Peroxynitrite homolyzes after (i) protonation, yielding hydroxyl ((*)OH) and nitrogen dioxide ((*)NO(2)) free radicals, and (ii) reaction with carbon dioxide (CO(2)), yielding carbonate radical anion (CO(3)(*)(-)) an...

Interactions between uric acid and physiologically relevant fluxes of nitric oxide ((?)NO) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of (?)NO, a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and alpha-tocopherol consumption, whi...

Previous reports proposed that peroxynitrite (ONOO-) oxidizes alpha-tocopherol (alpha-TOH) through a two-electron concerted mechanism. In contrast, ONOO- oxidizes phenols via free radicals arising from peroxo bond homolysis. To understand the kinetics and mechanism of alpha-TOH and gamma-tocopherol (gamma-TOH) oxidation in low-density lipoprotein (...

We have studied the role of three Mn(III)porphyrins differing in charge, alkyl substituent length and reactivity, on LDL exposed to low fluxes of peroxynitrite (PN) in the presence of uric acid. Mn(III)porphyrins (5 microM, MnTE-2-PyP(5+), MnTnOct-2-PyP(5+), and MnTCPP(3-)) plus uric acid (300 microM) inhibited cholesteryl ester hydroperoxide forma...

A key early event in the development of atherosclerosis is the oxidation of low density lipoprotein (LDL) via different mechanisms including free radical reactions with both protein and lipid components. Nitric oxide (⋅NO) is capable of inhibiting LDL oxidation by scavenging radical species involved in oxidative chain propagation reactions. Herein,...

Nitric oxide (*NO) is a free radical species that diffuses and concentrates in the hydrophobic core of low-density lipoprotein (LDL) to serve as a potent inhibitor of lipid oxidation processes. Peroxynitrite (PN), the product of the diffusion-limited reaction between *NO and superoxide (O2*-) represents a relevant mediator of oxidative modification...

Peroxynitrite (PN), the product of the diffusion-limited reaction between nitric oxide (*NO) and superoxide (O*-(2)), represents a relevant mediator of oxidative modifications in low-density lipoprotein (LDL). This work shows for the first time the simultaneous action of low-controlled fluxes of PN and *NO on LDL oxidation in terms of lipid and pro...

Copper binding to apolipoprotein B-100 (apo B-100) and its reduction by endogenous components of low-density lipoprotein (LDL) represent critical steps in copper-mediated LDL oxidation, where cuprous ion (Cu(I)) generated from cupric ion (Cu(II)) reduction is the real trigger for lipid peroxidation. Although the copper-reducing capacity of the lipi...

Atherosclerosis is one of the most common diseases and the principal cause of death in western civilization. The pathogenesis of this disease can be explained on the basis of the 'oxidative-modification hypothesis,' which proposes that low-density lipoprotein (LDL) oxidation represents a key early event. Nitric oxide (*NO) regulates critical lipid...

Atherosclerosis is one of the most common diseases and the principal cause of death in western civilization. The pathogenesis of this disease can be explained on the basis of the ‘oxidative-modification hypothesis,’ which proposes that low-density lipoprotein (LDL) oxidation represents a key early event. Nitric oxide (.NO) regulates critical lipid...

The partial amino acid sequence of the tetrameric isolectin B4 from Vicia villosa seeds has been determined by peptide analysis, and its three-dimensional structure solved by molecular replacement techniques and refined at 2.9 A resolution to a crystallographic R-factor of 21%. Each subunit displays the thirteen-stranded beta-barrel topology charac...

We report the development of an immuno-lectin-enzymatic assay (CA83.4) with the purpose of quantifying serum glycoproteins bearing Tn determinant (GalNAc alpha-O-Ser/Thr). An anti-Tn monoclonal antibody (83D4) is bound to the solid phase in order to capture glycoproteins. After the addition of a test sample, we used biotinylated isolectin B4 from V...

The Tn antigen (GaINAc-O-Ser/Thr) is one of the most specific human carcinoma associated structures. In order to measure soluble Tnglycoproteins, we have developed an immuno-lectin-enzymatic assay (CA83.4), in which a monoclonal antibody (83D4) is bound to the solid phase to capture glycoproteins bearing Tn determinant. After addition of test sampl...