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Introduction
My research is focused on studying the potential therapeutic effects of olive phenolic compounds on aging and neurodegenerative diseases. By using simple animal models, such as the nematode Caenorhabditis elegans, my main interest is to identify molecular and cellular mechanisms underlying the beneficial effects of these compounds, which could lead to the identification of potential targets in humans useful to develop anti-aging and neuroprotective therapies.
Additional affiliations
May 2012 - February 2016
Publications
Publications (41)
The capacity of Topoisomerase II (Topo II) to remove DNA catenations that arise after replication is essential to ensure faithful chromosome segregation. Topo II activity is monitored during G2 by a specific checkpoint pathway that delays entry into mitosis until the chromosomes are properly decatenated. Recently, we demonstrated that the mitotic d...
Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioact...
Catalytic inhibition of topoisomerase II during G2 phase delays onset of mitosis due to the activation of the so‐called decatenation checkpoint. This checkpoint is less known compared with the extensively studied G2 DNA damage checkpoint and is partially compromised in many tumor cells. We recently identified MCPH1 as a key regulator that confers c...
Parkinson's disease (PD) is a common neurodegenerative disorder involving α-synuclein (α-syn) aggregation, oxidative stress, dysregulation of redox metal homeostasis, and neurotoxicity. Different phenolic compounds with known antioxidant or antichelating properties have been shown to also interfere with aggregation of amyloid proteins and modulate...
Cellular checkpoints controlling entry into mitosis monitor the integrity of the DNA and delay mitosis onset until the alteration is fully repaired. However, this canonical response can weaken, leading to a spontaneous bypass of the checkpoint, a process referred to as checkpoint adaptation. Here, we have investigated the contribution of microcepha...
MCPH1 gene, mutated in primary microcephaly, regulates cell progression into mitosis. While this role has been extensively investigated in the context of DNA damage, its function during unperturbed cell cycles has been given less attention. Here we have analyzed the dynamics of chromosome condensation and cell cycle progression in MCPH1 deficient c...
In the kidney, tissue oxygen tension is comparatively low and this renders this organ more prone to hypoxic injury. In fact, hypoxia has a central role in the development and progression of renal disease. The recovery from this situation is dependent on the degree to which sublethally damaged cells restore normal function. The master regulator of t...
Numerosos estudios han demostrado la relación entre el estrés oxidativo/nitrosativo, la hipoxia y la disfunción renal. El hidroxitirosol (HT), principal polifenol del aceite de oliva, ejerce una acción antioxidante; sin embargo, aún no se ha estudiado su efecto en la hipoxia renal. En este sentido, nuestros resultados en células embrionarias humana...
Purpose:
We have previously reported that tyrosol (TYR) promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in vivo. In this study, we performed a whole-genome DNA microarray in order to narrow down the search for candidate genes or signaling pathways potentially i...
Background:
Successful combined antiretroviral therapy (cART) does not always result in complete CD4 T-cell recovery despite the effective control of HIV replication. Because telomere dysregulation can lead to an abnormal cell proliferation, we hypothesized that the lack of CD4 recovery may be related to telomere defects; We thus evaluated the ass...
The purpose of this study was to investigate whether the combination of oral quercetin (Q) supplementation and exercise prevents mitochondrial biogenesis. Four groups of Wistar rats were tested: quercetin-sedentary (Q-sedentary); quercetin-exercised (Q-exercised); no-quercetin-sedentary (NQ-sedentary); and no-quercetin-exercised (NQ-exercised). Tre...
We aimed to test exercise-induced adaptations on skeletal muscle when quercetin is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin exercised, placebo sedentary, and placebo exercised. Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups were supplemented with quercetin, via gavage, on alte...
Tyrosol [TYR, 2-(4-hydroxyphenyl)ethanol], one of the main phenols in olive oil and olive fruit, significantly strengthens resistance to thermal and oxidative stress in the nematode Caenorhabditis elegans and extends its lifespan. To elucidate the cellular functions regulated by TYR, we have used a proteomic procedure based on 2-DE coupled with MS...
Oxygen is essential for the survival of all aerobic organisms and particularly important to certain organs, such as the central nervous system (CNS). Among thecomplex metabolic reactions occurring during hypoxia, many are related to the formationof reactive oxygen and nitrogen species (ROS and RNS) to which the CNS is alsoparticularly vulnerable.RO...
Extra virgin olive oil (EVOO) consumption has been traditionally related to a higher longevity in the human population. EVOO effects on health are often attributed to its unique mixture of phenolic compounds with tyrosol and hydroxityrosol being the most biologically active. Although these compounds have been extensively studied in terms of their a...
In this work, the use of liquid chromatography coupled to electrospray time-of-flight mass spectrometry (LC-TOFMS) has been evaluated for the profiling of relatively low-molecular weight protein species in both genetically modified (GM) and non-GM maize. The proposed approach consisted of a straightforward sample fractionation with different water...
The physiological response to hypobaric hypoxia represents a complex network of biochemical pathways in which the nitrergic system plays an important role. Previous studies have provided evidence for an interplay between the hypoxia-inducible factor-1 (HIF-1) and poly(ADP-ribose) polymerase-1 (PARP-1) under hypoxia. Here, we evaluate the potential...
We previously reported that treatment with a single dose of deferoxamine (DFO), which acts as a hypoxic-mimetic agent, only induces reactive oxygen species (ROS) production in the presence of poly(ADP-ribose) polymerase (PARP-1). Given that mitochondria are one of the main sources of ROS, the present study was designed to assess the effect of DFO t...
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that once activated by genotoxic agents, modulates its own activity and that of several other nuclear proteins. The absence or pharmacological inhibition of this protein has been proven to be beneficial in the treatment of different diseases involving a hypoxic situation. We previously rep...
Aged individuals are more susceptible to hypoxic insults, but little is known about the response of the nitric oxide (NO) system to hypoxia in the senescent brain. We have analysed the effect of aging on the hypobaric hypoxia/reoxygenation NO synthase (NOS) expression and activity in the cerebral cortex. In aged animals, the absence of significant...
The effect of aging on basal and hypoxia/reoxygenation levels of both oxidative stress (protein carbonyl and TBARS) and antioxidative-enzyme activity (Cu/Zn-SOD; Mn-SOD; Catalase, CAT; Se-independent and Se-dependent glutathione peroxidase, GPX; glutathione transferase, GST and glutathione reductase, GR) has been studied in the cerebral cortex of a...
To analyze the relationship between perisinusoidal stellate cell (PSC) activation and the dietary fat quantity and composition in the treatment of hepatic steatosis.
Using an experimental rat model of steatosis based on the intake of a hyperlipidic diet (14% fat as olive oil or sunflower oil, HL-O and HL-S, respectively), we analyzed the liver's ca...
Aged brain shows reduced biological plasticity to meet emergency conditions such as ischemia, a process in which nitric oxide (NO) and apoptosis have been shown to play important roles. Using a model of transient global ischemia, we have analyzed the NO system and the p53, bax and bcl-2 response in the cerebral cortex of aged rats. Although immedia...
Nitrate, nitrite, and other nitroso compounds (NOxs) had been proposed as possible nitric oxide (NO) storage molecules. The present work examines, by means of chemiluminescence analysis, changes in NOx serum levels in rats 1 h before and 24, 48, and 72 h after exposure to acute hypobaric hypoxia (HH; barometric pressure [P(B)] 225 mmHg, oxygen part...
p53 deficiency confers resistance to doxo (doxorubicin), a clinically active and widely used antitumour anthracycline antibiotic. The purpose of the present study was to investigate the reversal mechanism of doxo resistance by the potent PARP [poly(ADP-ribose) polymerase] inhibitor ANI (4-amino-1,8-naphthalimide) in the p53-deficient breast cancer...
This study examines the expression and cellular distribution pattern of nitric oxide synthase (NOS) isoforms, nitrotyrosine-derived complexes, and the nitric oxide (NO) production in the cerebellum of rats with cirrhosis induced by thioacetamide (TAA). The results showed local changes in the tissue distribution pattern of the NOS isoforms and nitra...
Aging is associated with increased oxidant generation. One mechanism involved in the defense of oxidative products is the family of glutathione transferases (GST). We have analyzed the activity, distribution and expression of GSTP1 and GSTA4 isoenzymes in the cerebral cortex and cerebellum of young, adult and aged rats. The total GST activity, meas...
This work examines the age-related changes of the NO pathway in the central nervous system (CNS), analyzing nitric oxide synthase (NOS) isoform expression, the level of nitrotyrosine-modified proteins, and the NOS activity in the cerebral cortex, decorticated brain (basal ganglia, thalamus, hypothalamus, tegtum and tegmentum) and cerebellum of youn...