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Dive into the research topics where Pablo V. Escribá is active.

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Featured researches published by Pablo V. Escribá.


Proceedings of the National Academy of Sciences of the United States of America | 2008

Oleic acid content is responsible for the reduction in blood pressure induced by olive oil

Silvia Terés; Gwendolyn Barceló-Coblijn; M. Benet; Rafael Álvarez; R. Bressani; John E. Halver; Pablo V. Escribá

Numerous studies have shown that high olive oil intake reduces blood pressure (BP). These positive effects of olive oil have frequently been ascribed to its minor components, such as α-tocopherol, polyphenols, and other phenolic compounds that are not present in other oils. However, in this study we demonstrate that the hypotensive effect of olive oil is caused by its high oleic acid (OA) content (≈70–80%). We propose that olive oil intake increases OA levels in membranes, which regulates membrane lipid structure (HII phase propensity) in such a way as to control G protein-mediated signaling, causing a reduction in BP. This effect is in part caused by its regulatory action on G protein-associated cascades that regulate adenylyl cyclase and phospholipase C. In turn, the OA analogues, elaidic and stearic acids, had no hypotensive activity, indicating that the molecular mechanisms that link membrane lipid structure and BP regulation are very specific. Similarly, soybean oil (with low OA content) did not reduce BP. This study demonstrates that olive oil induces its hypotensive effects through the action of OA.


Journal of Cellular and Molecular Medicine | 2008

Membranes: a meeting point for lipids, proteins and therapies

Pablo V. Escribá; José M. González-Ros; Félix M. Goñi; Paavo K. J. Kinnunen; László Vígh; Lissete Sánchez-Magraner; Asia M. Fernández; Xavier Busquets; Ibolya Horváth; Gwendolyn Barceló-Coblijn

•  Introduction •  Membrane lipid composition •  Membrane lipid structure •  Membrane lipid organization ‐  Why so many different lipids? ‐  Lipid mixing and demixing ‐  Lateral pressure ‐  Surface electrostatics •  Role of lipids in cell functions •  Lipid influence in transmembrane protein function ‐  Prokaryotic potassium channel (KcsA) ‐  Mechanosensitive channels ‐  Voltage‐gated potassium channel (KvAP) ‐  Nicotinic acetylcholine receptor (nAcChR) ‐  G protein‐coupled receptors ‐  Other examples •  Non‐permanent proteins in membranes ‐  Proteins that interact reversibly with the bilayers ‐  Proteins that interact irreversibly with the bilayers ‐  Proteins that interact weakly with the membrane ‐  Proteins that interact strongly with the membrane ‐  G proteins and their interactions with membranes ‐  Small monomeric G proteins: the Ras and Ras‐like family ‐  Protein kinase C •  Membrane microdomains and lipid mediators in the control of heat‐shock protein response ‐  Stress sensing and signalling: the membrane sensor theory ‐  Hsp signalling in cancer and diabetes ‐  The role of membrane microdomains ‐  Lipid mediators of the stress response •  A subpopulation of Hsps can interact with and translocate through membranes ‐  Hsp90 in eukaryotic membranes ‐  Hsp70 in cell membranes ‐  Hsp27‐membrane interactions ‐  Secreted Hsps ‐  Representative cases where Hsps interact with membranes or release from the cells •  Concluding remarks


Journal of Neurochemistry | 1999

Up-Regulation of Immunolabeled α2A-Adrenoceptors, Gi Coupling Proteins, and Regulatory Receptor Kinases in the Prefrontal Cortex of Depressed Suicides

J.A. García-Sevilla; Pablo V. Escribá; Andrés Ozaita; Romano La Harpe; Claude Walzer; Ariel Eytan; José Guimón

Abstract : Suicide and depression are associated with an increased density of α2‐adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein‐coupled receptor kinases, GRKs), which work in concert with the receptors. In this study we quantitated in parallel the levels of immunolabeled α2A‐adrenoceptors and associated regulatory proteins in brains of suicide and depressed suicide victims. Specimens of the prefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and 31 control subjects. Levels of α2A‐adrenoceptors, Gα1/2 proteins, and GRK 2/3 were assessed by immunoblotting techniques by using specific polyclonal antisera and the immunoreactive proteins were quantitated by densitometry. Increased levels of α2A‐adrenoceptors (31‐40%), Gα1/2 proteins (42‐63%), and membrane‐associated GRK 2/3 (24‐32%) were found in the prefrontal cortex of suicide victims and antidepressantfree depressed suicide victims. There were significant correlations between the levels of GRK 2/3 (dependent variable) and those of α2A‐adrenoceptors and Gα1/2 proteins (independent variables) in the same brain samples of suicide victims (r = 0.56, p = 0.008) and depressed suicide victims (r = 0.54, p = 0.041). Antemortem antidepressant treatment was associated with a significant reduction in the levels of Gα1/2 proteins (32%), but with modest decreases in the levels of α2A‐adrenoceptors (6%) and GRK 2/3 (18%) in brains of depressed suicide victims. The increased levels in concert of α2A‐adrenoceptors, Gα1/2 proteins, and GRK 2/3 in brains of depressed suicide victims support the existence of supersensitive α2A‐adrenoceptors in subjects with major depression.


Neuropsychopharmacology | 2004

Increased mRNA expression of α2A-adrenoceptors, serotonin receptors and μ-opioid receptors in the brains of suicide victims

Pablo V. Escribá; Andrés Ozaita; Jesús A. García-Sevilla

The development of new therapies for the treatment of psychiatric disorders requires an in-depth knowledge of the molecular bases underlying these pathologies, which remain largely unknown. Alterations in adrenoceptors, serotonin receptors, and other G protein-coupled receptors (GPCRs) have been associated with suicide and depression. However, to date, there is little information about mRNA expression of the GPCRs in the frontal cortex of suicide victims. Our goal was to study the expression in the brain of these receptors. For this purpose, we measured mRNA levels by RT-PCR. We found that the expressions of α2A-adrenoceptors, 5-HT1A, 5-HT2A serotonin receptors, and μ-opioid receptors were elevated in the post-mortem brains of these suicide victims with respect to matched controls. Moreover, in the case of α2A-adrenoceptors (the only for which these data were available), a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of this receptor was not influenced by post-translational regulatory mechanisms. In addition, the degree of adrenoceptor and 5-HT receptor expressions appeared to be correlated in the brains of suicide victims and control subjects. Alterations in the expression of adrenoceptors, serotonin, and opioid receptors indicate that these signaling proteins might be related to the etiopathology of suicidal and depressive behaviors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. The results also suggest that these receptors could share common regulatory mechanisms.


Biochimica et Biophysica Acta | 2014

The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health

Maitane Ibarguren; David J. López; Pablo V. Escribá

This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimers and Parkinsons disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cells Physiology, Pathology and Therapy.


British Journal of Pharmacology | 1993

Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down‐regulates non‐adrenoceptor [3H]‐idazoxan binding sites in the rat brain

Gabriel Olmos; Ane M. Gabilondo; Antonio Miralles; Pablo V. Escribá; Jesús A. García-Sevilla

1 The binding of [3H]‐idazoxan in the presence of 10−6m (−)‐adrenaline was used to quantitate non‐adrenoceptor idazoxan binding sites (NAIBS) in the rat brain after treatment with various psychotropic drugs. 2 Chronic treatment (14 days) with the monoamine oxidase (MAO) inhibitors clorgyline (0.3–10 mg kg−1, i.p.) and pargyline (10 mg kg−1, i.p.), but not with Ro 41–1049 (1 mg kg−1, i.p.), markedly decreased (30–50%) the density of NAIBS in the cerebral cortex without any apparent change in the affinity of the radioligand. 3 Acute (1 day) and/or chronic treatments (14 days) with other psychotropic drugs such as desipramine (3 mg kg−1, i.p.), cocaine (10 mg kg−1, i.p.), reserpine (0.12 mg kg−1, s.c.), haloperidol (1 mg kg−1, i.p.) and diazepam (10 mg kg−1, i.p.) did not alter the density of NAIBS in the cerebral cortex. 4 In vitro, the propargylamines clorgyline, pargyline and deprenyl displaced the binding of [3H]‐idazoxan to NAIBS from two distinct sites, but only clorgyline displayed an apparent very high affinity for a relevant population of NAIBS (KiH = 40 pm; KiL = 10.6 μm). The structurally diverse MAO inhibitors Ro 16–6491 (selective for MAO‐B) and Ro 41–1049 (selective for MAO‐A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]‐idazoxan to NAIBS monophasically and with very low potencies. As expected, the MAO inhibitors clorgyline and Ro 41–1049 displaced the binding of [3H]‐Ro 41–1049 to MAO‐A monophasically and with high potencies (Ki values: 0.18 nm and 22 nm, respectively). In contrast, idazoxan displayed very low affinity (Ki = 40 μm) against the binding of [3H]‐Ro 41–1049 to MAO‐A. These results disprove a direct interaction between [3H]‐idazoxan and the enzyme MAO. 5 Preincubation of cortical membranes with clorgyline (10−9 m or 10−6 m for 30 min) or pargyline (10−6 m or 10−5 m for 30 min), reduced by 30–50% and by 17–30%, respectively, the total density of NAIBS without any apparent change in the affinity of the radioligand. Preincubation with 10−6 m clorgyline did not alter the affinity of cirazoline for the two populations of NAIBS, but reduced by 60% the binding of [3H]‐idazoxan to the high affinity site without affecting the binding of the radioligand to the low affinity site. These results indicate that the two MAO inhibitors irreversibly block the binding of [3H]‐idazoxan to NAIBS. 6 In vivo, however, various acute treatments with clorgyline (1–20 mg kg−1, i.p.) for different time intervals (6–48 h) did not alter the density of NAIBS. In vivo, only very high doses of clorgyline (40 and 80 mg kg−1, i.p.) induced modest decreases (21–28%) in the density of NAIBS in the cerebral cortex. 7 Together the results indicate that the irreversible binding of clorgyline and pargyline to NAIBS found in vitro does not fully explain the marked decreases in the density of NAIBS found in vivo after the chronic treatments. It is suggested that the down‐regulation of NAIBS induced in vivo by clorgyline and pargyline, through a direct or indirect mechanism, may have functional implications.


Proceedings of the National Academy of Sciences of the United States of America | 2011

Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy

Gwendolyn Barceló-Coblijn; Maria Laura Martin; Maria Antònia Noguera-Salvà; Francisca Guardiola-Serrano; Anja Lüth; Burhard Kleuser; John E. Halver; Pablo V. Escribá

The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.


Hypertension | 2003

Alteration of Lipids, G Proteins, and PKC in Cell Membranes of Elderly Hypertensives

Pablo V. Escribá; José M. Sánchez-Domı́nguez; Regina Alemany; Javier S. Perona; Valentina Ruiz-Gutiérrez

Abstract—In this study, we quantified the levels of lipids and signaling proteins in erythrocyte membranes from elderly normotensive and hypertensive subjects. In hypertensive subjects, the cholesterol/phospholipid ratio increased significantly in erythrocyte membranes, owing to the reduction of phospholipid levels concomitant with a rise in the levels of cholesterol. In addition, differences were also found in the amount of fatty acids in both phospholipid and cholesterol esters. Erythrocyte membranes from hypertensive subjects contained higher levels of monounsaturated and lower levels of polyunsaturated fatty acids. On the other hand, signaling proteins such as G proteins and protein kinase C have been implicated in the control of blood pressure. Previous studies have shown that the cellular localization and the activity of these proteins are modulated by the type and the abundance of membrane lipids. For this reason, we assessed the levels of these signaling molecules in the membrane. We found that the levels of membrane-associated (active/preactive) G proteins (G&agr;i, G&agr;o, and G&bgr;) and protein kinase C were significantly reduced in hypertensive subjects. We believe that these alterations could be related to the etiopathology of hypertension in elderly subjects or alternatively may correspond to adaptive compensatory mechanisms.


Biochimica et Biophysica Acta | 2008

Membrane interactions of G proteins and other related proteins

Oliver Vögler; Juana M. Barceló; Catalina Ribas; Pablo V. Escribá

Guanine nucleotide-binding proteins, G proteins, propagate incoming messages from receptors to effector proteins. They switch from an inactive to active state by exchanging a GDP molecule for GTP, and they return to the inactive form by hydrolyzing GTP to GDP. Small monomeric G proteins, such as Ras, are involved in controlling cell proliferation, differentiation and apoptosis, and they interact with membranes through isoprenyl moieties, fatty acyl moieties, and electrostatic interactions. This protein-lipid binding facilitates productive encounters of Ras and Raf proteins in defined membrane regions, so that signals can subsequently proceed through MEK and ERK kinases, which constitute the canonical MAP kinase signaling cassette. On the other hand, heterotrimeric G proteins undergo co/post-translational modifications in the alpha (myristic and/or palmitic acid) and the gamma (farnesol or geranylgeraniol) subunits. These modifications not only assist the G protein to localize to the membrane but they also help distribute the heterotrimer (Galphabetagamma) and the subunits generated upon activation (Galpha and Gbetagamma) to appropriate membrane microdomains. These proteins transduce messages from ubiquitous serpentine receptors, which control important functions such as taste, vision, blood pressure, body weight, cell proliferation, mood, etc. Moreover, the exchange of GDP by GTP is triggered by nucleotide exchange factors. Membrane receptors that activate G proteins can be considered as such, but other cytosolic, membranal or amphitropic proteins can accelerate the rate of G protein exchange or even activate this process in the absence of receptor-mediated activation. These and other protein-protein interactions of G proteins with other signaling proteins are regulated by their lipid preferences. Thus, G protein-lipid interactions control the features of messages and cell physiology.


Annals of the New York Academy of Sciences | 1999

Imidazoline Receptors and Human Brain Disordersa

J.A. García-Sevilla; Pablo V. Escribá; José Guimón

ABSTRACT: Major depression, opioid addiction, neurodegenerative diseases, and glial tumors are associated with disturbances of imidazoline receptors (IR) in the human brain. In depression, the level of a 45‐kD IR protein (putative I1‐IR) is increased in the brain of suicide victims (51%) and in platelets of depressed patients (40%). The density of platelet I1‐IR ([125I]‐p‐iodoclonidine binding) is also increased in depression (135%). The 29/30‐kD IR protein (putative I2B‐IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B‐IR ([3H]idazoxan binding). Antidepressant drugs induce downregulation of 45‐kD IR protein and I1‐sites in platelets of depressed patients and upregulation of I2‐sites in rat brain. The densities of I2B‐IR and the related 29/30‐kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I2B‐IR is increased in Alzheimers disease (63%) and decreased in Huntingtons disease (56%). Brain I2B‐IR is not altered in Parkinsons disease. The level of I2‐IR in glial tumors is increased (two fivefold) in parallel with the abundance of the related 29/30‐kD IR protein (39%), whereas the level of 45‐kD IR protein is decreased (39%). The possible functional relevance of these findings in the context of the pathogenesis of these disorders remains to be elucidated.

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Dive into the Pablo V. Escribá's collaboration.

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Xavier Busquets

University of the Balearic Islands

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Silvia Terés

University of the Balearic Islands

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Jesús A. García-Sevilla

University of the Balearic Islands

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Gwendolyn Barceló-Coblijn

University of the Balearic Islands

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Francisca Barceló

University of the Balearic Islands

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Victoria Lladó

University of the Balearic Islands

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David J. López

University of the Balearic Islands

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Jesús Prades

University of the Balearic Islands

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Rafael Álvarez

University of the Balearic Islands

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