Eduardo Muñoz - Academia.edu (original) (raw)

Papers by Eduardo Muñoz

Biochimica et biophysica acta, 2014

The N-acyl conjugates of amino acids and neurotransmitters (NAANs) are a class of endogenous lipi... more The N-acyl conjugates of amino acids and neurotransmitters (NAANs) are a class of endogenous lipid messengers that are expressed in the mammalian central and peripheral nervous system. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that plays a key role in the cellular adaptation to hypoxia and ischemia, and hypoxic preconditioning through HIF-1α has been shown to be neuroprotective in ischemic models. This study showed that N-acyl-dopamines induce HIF-1α stabilization on human primary astrocytes and neurons as well as in transformed cell lines. N-arachidonoyl-dopamine (NADA)-induced HIF-1α stabilization depends on the dopamine moiety of the molecule and is independent of cannabinoid receptor-1 (CB1) and transient receptor potential vanilloid type I (TRPV1) activation. NADA increases the activity of the E3 ubiquitin ligase seven in absentia homolog-2 (SIAH2), inhibits prolyl-hydroxylase-3 (PHD3) and stabilizes HIF-1α. NADA enhances angiogenesis in endothelial vascula...

Cell Death & Differentiation, 1999

Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMO... more Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMOR) system and induces apoptosis in transformed cells. Using a cytofluorimetric approach we have determined that capsaicin induces a rapid increase of reactive oxygen species (ROS) followed by a subsequent disruption of the transmembrane mitochondrial potential (DC m) and DNA nuclear loss in transformed cell lines and in mitogen activated human T cells. This apoptotic pathway is biochemically different from the typical one induced by either ceramide or edelfosine where, in our system, the DC m dissipation precedes the generation of reactive oxygen species. Neither production of ROS nor apoptosis was found in capsaicin-treated resting T cells where the activity of the PMOR system is minimal when compared with mitogen activated or transformed T cells. Capsaicin also induces Ca 2+ mobilization in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS generation or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and that the apoptotic pathway may be separated from the one that mobilizes calcium. Moreover, we present data for the implication of a possible vanilloid receptor in calcium mobilization, but not in ROS generation. These results provide evidence that the PMOR system may be an interesting target to design antitumoral and anti-inflammatory drugs.

Journal of Neuroimmunology, 2006

Inhibition of neuronal cyclooxygenase-2 (COX-2) and hence prostaglandin E 2 (PGE 2) synthesis by ... more Inhibition of neuronal cyclooxygenase-2 (COX-2) and hence prostaglandin E 2 (PGE 2) synthesis by non-steroidal anti-inflammatory drugs has been suggested to protect neuronal cells in a variety of pathophysiological situations including Alzheimer's disease and ischemic stroke. Ascorbic acid (vitamin C) has also been shown to protect cerebral tissue in a variety of experimental conditions, which has been attributed to its antioxidant capacity. In the present study, we show that ascorbic acid dose-dependently inhibited interleukin-1β (IL-1β)-mediated PGE 2 synthesis in the human neuronal cell line, SK-N-SH. Furthermore, in combination with aspirin, ascorbic acid augmented the inhibitory effect of aspirin on PGE 2 synthesis. However, ascorbic acid had no synergistic effect along with other COX inhibitors (SC-58125 and indomethacin). The inhibition of IL-1β-mediated PGE 2 synthesis by ascorbic acid was not due to the inhibition of the expression of COX-2 or microsomal prostaglandin E synthase (mPGES-1). Rather, ascorbic acid dose-dependently (0.1-100 µM) produced a significant reduction in IL-1β-mediated production of 8-iso-prostaglandin F 2α (8iso-PGF 2α), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE 2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress. Our results provide in vitro evidence that the neuroprotective effects of ascorbic acid may depend, at least in part, on its ability to reduce neuronal COX-2 activity and PGE 2 synthesis, owing to its antioxidant properties. Further, these experiments suggest that a combination of aspirin with ascorbic acid constitutes a novel approach to render COX-2 more sensitive to inhibition by aspirin, allowing an anti-inflammatory therapy with lower doses of aspirin, thereby avoiding the side effects of the usually high dose aspirin treatment.

Journal of Neuroinflammation, 2007

Background Neuroinflammatory responses are triggered by diverse ethiologies and can provide eithe... more Background Neuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti-inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E2 (PGE2) and 8-iso-prostaglandin F2α (8-iso-PGF2α) production by lipopolysaccharide (LPS)-activated primary...

Objective: To review some of the main aspects of the process of couples therapy. Development: The... more Objective: To review some of the main aspects of the process of couples therapy. Development: Therapy begins with an initial assessment of the family, its characteristics, family dynamics and the factors that determine its functionality. This will then be used as a guide for appro- aching the couples therapy. Important topics to consider will be the couple's conformation, evaluation, course

British journal of cancer, 1999

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (... more Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may i...

Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to... more Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to the isolation of the new prenylbisabolane 3, whose structure was assessed by spectroscopic methods. The corresponding known enone 4 and the eudesmane sesquiterpene 2 were also obtained. Compound 3 proved active in selectively inhibiting the induction of NF-κB by tumor necrosis factor-α in T cells.

Journal of neuroinflammation, Jan 18, 2005

BACKGROUND: Previous studies suggest that the cyclooxygenase-2 (COX-2) inhibitor nimesulide has a... more BACKGROUND: Previous studies suggest that the cyclooxygenase-2 (COX-2) inhibitor nimesulide has a remarkable protective effect against different types of brain injury including ischemia. Since there are no reports on the effects of nimesulide on permanent ischemic stroke and because most cases of human stroke are caused by permanent occlusion of cerebral arteries, the present study was conducted to assess the neuroprotective efficacy of nimesulide on the cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion (pMCAO) in the rat. METHODS: Ischemia was induced by permanent occlusion of the middle cerebral artery in rats, via surgical insertion of a nylon filament into the internal carotid artery. Infarct volumes (cortical, subcortical and total) and functional recovery, assessed by neurological score evaluation and rotarod performance test, were performed 24 h after pMCAO. In initial experiments, different doses of nimesulide (3, 6 and 12 mg...

Journal of Medicinal Chemistry, 2014

The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investiga... more The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E 2 synthase (mPGES)-1 and 5lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure− activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (i.e., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-κB, nuclear factorerythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.

Introduction: In 1880, the French psychiatrist Jules Cotard described several patients who suffer... more Introduction: In 1880, the French psychiatrist Jules Cotard described several patients who suffered from a syndrome referred to as délire de négation. This relatively rare condition is characterized by the presence of nihilist delusions in which the person who has it thinks "it is dead or the world does not exist". Method: This article reports the case of a patient

Sol-gel zirconia precursor, zirconium n-butoxide in ter-butanol, was irradiated with 1.3 MeV elec... more Sol-gel zirconia precursor, zirconium n-butoxide in ter-butanol, was irradiated with 1.3 MeV electrons to a dose of 330 KGy. Gelling was instantaneously produced when an aqueous solution of sulfuric, hydrochloric or acetic acid was added to the irradiated solution; no hydrolysis catalyst was required. Samples were characterized with X-ray powder diffraction, infrared spectroscopy, and electron paramagnetic resonance. The electron irradiation accelerated hydrolysis and condensation, which avoided the stabilization of the tetragonal phase via carboxyls, and decreased the capability of sulfate ions to stabilize it. These results suggest that the stabilization of the tetragonal phase of sol-gel zirconia via carboxyl and sulfate ions depends on their diffusion in the sol.

ChemInform, 2009

Other bioactive products U 1300 Clavaminols G-N, Six New Marine Sphingoids from the Mediterranean... more Other bioactive products U 1300 Clavaminols G-N, Six New Marine Sphingoids from the Mediterranean Ascidian Clavelina phlegraea. -The biological activities of clavaminols are studied, but none of the compounds shows significant cytotoxicity. -(AIELLO, A.; FATTORUSSO, E.; GIORDANO, A.; MENNA*, M.; NAVARRETE, C.; MUNOZ, E.; Tetrahedron 65 (2009) 22, 4384-4388; Dip. Chim. Sostanze Nat., Univ. "Federico II", I-80131 Napoli, Italy; Eng.) -Bartels 38-208

Journal of Molecular Cell Biology, 2012

The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to th... more The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3, which in turn increases the stability of hypoxia-inducible factor (HIF)-1α. In the present study, we identify the serine/threonine kinase DYRK2 as SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119). Phosphomimetic and phospho-mutant forms of SIAH2 exhibit different subcellular localizations and consequently change in PHD3 degrading activity. Accordingly, phosphorylated SIAH2 is more active than the wild-type E3 ligase and shows an increased ability to trigger the HIF-1α-mediated transcriptional response and angiogenesis. We also found that SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation. Hypoxic conditions cause a SIAH2-dependent DYRK2 polyubiquitination and degradation which ultimately also results in an impaired SIAH2 phosphorylation. Similarly, DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors.

Veterinary Microbiology, 2012

BM, 2012. Characterization and clonal grouping of pathogenic Escherichia coli isolated from intes... more BM, 2012. Characterization and clonal grouping of pathogenic Escherichia coli isolated from intestinal contents of diarrheic piglets in Villa Clara province, Cuba, according to their antibiotic resistance and ERIC-PCR profiles. Veterinary Microbiology, 154:425-8. Chapter 3| 67

Thin Solid Films, 2010

In this work morphological, structural and photoelectrochemical properties of n-type α-Fe 2 O 3 (... more In this work morphological, structural and photoelectrochemical properties of n-type α-Fe 2 O 3 (hematite) thin films synthetized by means of two different electrochemical procedures: potential cycling electrodeposition (PC) and potential pulsed electrodeposition (PP) have been studied. The X-ray diffraction measurements showed that the films obtained after a thermal treatment at 520°C present a nanocrystalline character. Scanning electron microscopy allowed finding that hematite films obtained by PP technique exhibit nanostructured morphology. The electrochemical and capacitance (Mott-Schottky and parallel capacitance) measurements showed that when in the PC and PP procedures the anodic limit E λ,A is being made more anodic, a decrease of the majority carriers concentration (N D ) and the surface states number has been observed. The photovoltammetry measurements indicated that the hematite films formed with the PP technique present a photocurrent one order of magnitude higher than the ones exhibited by the iron oxide films formed by PC. For instance, PP hematite films exhibit photovoltaic conversion efficiencies of 0.96% which are 2.5 times higher than the corresponding to the PC ones (0.38%). The maximum incident photon-to-current efficiency measured at λ = 370 and 600 nm was observed for hematite films grown by the PP procedure. By means of the photocurrent transient technique a decrease in the recombination process for those samples synthesized by PP was observed. The results obtained are discussed considering the influence of the anodic limit of the potential employed during the preparation of the iron oxyhydroxide (β-FeOOH) precursor film, all of this related to a decrease of the oxygen defects in this material and to a decrease of Fe(II) amount that is formed during the electrodeposition process.

Thin Solid Films, 2009

In this study we examined the rhenium electrodeposition process onto p-Si(100) from acidic media.... more In this study we examined the rhenium electrodeposition process onto p-Si(100) from acidic media. The study was carried out by means of cyclic voltammetry and the potential-steps method from which the corresponding nucleation and growth mechanism were determined. Both methods were performed under illumination using a solar simulator for electron photogeneration. A 3D progressive nucleation, diffusioncontrolled growth of rhenium films was found. Likewise, a morphologic analysis was completed for the deposits obtained at different potential values by means of atomic force microscopy. An energetic characterization through capacitance measurements (Mott-Schottky plots and parallel capacitance) of the p-Si/NO 3 − and p-Si/Re/NO 3 − interfaces was done.

The Journal of Physical Chemistry B, 2006

In this study, we examined the influence of illumination and the presence of poly(ethylene oxide)... more In this study, we examined the influence of illumination and the presence of poly(ethylene oxide) (PEO) as an additive for the copper electrodeposition process onto n-Si(100). The study was carried out by means of cyclic voltammetry (CV) and the potential steps method, from which the corresponding nucleation and growth mechanism (NGM) were determined. Likewise, a morphologic analysis of the deposits obtained at different potential values by means of atomic force microscopy (AFM) was carried out. In a first stage, Mott-Schottky measurements so as to characterize the energetics of the semiconductor/electrolyte interface were made. Also, parallel capacity measurements were carried out in order to determine the surface state density of the substrate. It was found that when PEO concentration is increased, the number of these surface states decreases. The CV results indicated that the presence of PEO inhibits the photoelectrochemical reaction of oxide formation on the surface of the semiconductor. This allows a decrease in the overpotential associated with the electrodeposition process. The analysis of the j/t transients shows that the NGM corresponds to progressive three-dimensional (3D) diffusional controlled (PN3D Diff ), which was confirmed by the AFM technique. Neither illumination nor the presence of PEO changes the mechanisms. Their influence is in that they diminish the size of the nuclei and the speed with which these are formed, which produces a more homogeneous electrodeposit.

Tetrahedron, 2009

An exhaustive examination of the chemical constituents of the Mediterranean ascidian Clavelina ph... more An exhaustive examination of the chemical constituents of the Mediterranean ascidian Clavelina phlegraea led to the isolation of clavaminols G-N (1-6), a new series of amino alcohols, which expand the family of modified marine sphingoids. Structures of the novel compounds 1-6 have been elucidated by spectroscopic analysis and chemical derivatization; bioactivities of compounds 1-6 have also been investigated and comparison of their pharmacological properties with those of previously isolated clavaminols A-F allowed us to perform an assessment of simple structure-activity relationships.