14 results on '"López‐Gambero, Antonio Jesús"'
Search Results
2. Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance
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Medina-Vera, Dina, primary, López-Gambero, Antonio Jesús, additional, Navarro, Juan Antonio, additional, Sanjuan, Carlos, additional, Baixeras, Elena, additional, Decara, Juan, additional, and de Fonseca, Fernando Rodríguez, additional
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- 2023
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3. Sex-based differences in IGF1 signaling pathways in response to PAPP-A2 deficiency
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Navarro, Juan Antonio, primary, López-Gambero, Antonio Jesús, additional, Fernández-Arjona, María del Mar, additional, de Ceglia, Marialuisa, additional, Rubio, Leticia, additional, de Fonseca, Fernando Rodríguez, additional, Barrios, Vicente, additional, Chowen, Julie A., additional, Argente, Jesús, additional, Perez, Juan Suarez, additional, and Rivera, Patricia, additional
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- 2023
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4. d-Pinitol promotes tau dephosphorylation through a cyclin-dependent kinase 5 regulation mechanism: A new potential approach for tauopathies?
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Medina‐Vera, Dina, Navarro, Juan Antonio, Rivera, Patricia, Rosell‐Valle, Cristina, Gutiérrez‐Adán, Alfonso, Sanjuan, Carlos, López‐Gambero, Antonio Jesús, Tovar, Rubén, Suárez, Juan, Pavón, Francisco Javier, Baixeras, Elena, Decara, Juan, Rodríguez de Fonseca, Fernando, Medina-Vera, Dina, Rosell-Valle, Cristina, Gutiérrez-Adán, Alfonso, and López-Gambero, Antonio Jesús
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NERVE tissue proteins ,LEPTIN ,CYCLIN-dependent kinases ,RATS ,RESEARCH funding ,NEURODEGENERATION ,MICE ,PHOSPHORYLATION ,ANIMALS ,INOSITOL - Abstract
Background and Purpose: Recent evidence links brain insulin resistance with neurodegenerative diseases, where hyperphosphorylated tau protein contributes to neuronal cell death. In the present study, we aimed to evaluate if d-pinitol inositol, which acts as an insulin sensitizer, affects the phosphorylation status of tau protein.Experimental Approach: We studied the pharmacological effect of d-pinitol on insulin signalling and tau phosphorylation in the hippocampus of Wistar and Zucker rats. To this end, we evaluated by western blotting the Akt pathway and its downstream proteins as being one of the main insulin-mediator pathways. Also, we explored the functional status of additional kinases phosphorylating tau, including PKA, ERK1/2, AMPK and CDK5. We utilized the 3xTg mouse model as a control for tauopathy, since it carries tau mutations that promote phosphorylation and aggregation.Key Results: Surprisingly, we discovered that oral d-pinitol treatment lowered tau phosphorylation significantly, but not through the expected kinase GSK-3 regulation. An extensive search for additional kinases phosphorylating tau revealed that this effect was mediated through a mechanism dependent on the reduction of the activity of the CDK5, affecting both its p35 and p25 subunits. This effect disappeared in leptin-deficient Zucker rats, uncovering that the association of leptin deficiency, obesity, dyslipidaemia and hyperinsulinaemia abrogates d-pinitol actions on tau phosphorylation. The 3xTg mice confirmed d-pinitol effectiveness in a genetic AD-tauopathy.Conclusion and Implications: The present findings suggest that d-pinitol, by regulating CDK5 activity through a decrease of CDK5R1, is a potential drug for developing treatments for neurological disorders such as tauopathies. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases
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Decara, Juan, Rivera, Patricia, López-Gambero, Antonio Jesús, Serrano, Antonia, Pavón, Francisco Javier, Baixeras, Elena, Rodríguez de Fonseca, Fernando, Suárez, Juan, [Decara,J, López-Gambero,AJ, Serrano,A, Pavón,FJ, Rodríguez de Fonseca,F, Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Rivera,P] Departamento de Endocrinología, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Pavón,FJ] Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) and UGC del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. [Baixeras,E] Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Málaga, IBIMA, Málaga, Spain., This study was supported by the following research projects and programs: Proyecto de Investigación en Salud 'PI-0139-2018' funded by Consejerı́a de Salud y Familias, Junta de Andalucı́a, 'DTS19/00125' funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Regional Development Fund (ERDF) 'A way to make Europe', Proyecto de Investigación en Salud 'PI19/01577' funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Regional Development Fund (ERDF) 'A way to make Europe', and AS and JS hold 'Miguel Servet' research contracts (CP14/00173 and CPII17/00024 respectively) from the ISCIII and co-funded by European Social Fund 'Investing in your future' PR holds a 'Sara Borrell' research contract (CD16/00067) from the ISCIII and co-funded by European Social Fund 'Investing in your future' FP holds a 'Programa Nicolás Monardes' contract (C1-0049-2019) from Servicio Andaluz de Salud, Junta de Andalucía.
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Enfermedades inflamatorias del intestino ,Chemicals and Drugs::Pharmaceutical Preparations [Medical Subject Headings] ,Inflammatory bowel diseases ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors [Medical Subject Headings] ,Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands [Medical Subject Headings] ,Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases [Medical Subject Headings] ,Crohn's disease ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors::PPAR gamma [Medical Subject Headings] ,Ulcerative colitis ,Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism [Medical Subject Headings] ,Colitis ulcerosa ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::NF-kappa B [Medical Subject Headings] ,Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Colitis, Ulcerative [Medical Subject Headings] ,PPARg ,Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease [Medical Subject Headings] ,Enfermedad de Crohn ,Receptores activados del proliferador del peroxisoma ,PPARa ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings] ,Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings] ,PPARb/d - Abstract
The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that promote ligand-dependent transcription of target genes that regulate energy production, lipid metabolism, and inflammation. The PPAR superfamily comprises three subtypes, PPARα, PPARγ, and PPARβ/δ, with differential tissue distributions. In addition to their different roles in the regulation of energy balance and carbohydrate and lipid metabolism, an emerging function of PPARs includes normal homeostasis of intestinal tissue. PPARα activation represses NF-κB signaling, which decreases the inflammatory cytokine production by different cell types, while PPARγ ligands can inhibit activation of macrophages and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Il-1β. In this regard, the anti-inflammatory responses induced by PPAR activation might restore physiopathological imbalances associated with inflammatory bowel diseases (IBD). Thus, PPARs and their ligands have important therapeutic potential. This review briefly discusses the roles of PPARs in the physiopathology and therapies of the most important IBDs, ulcerative colitis (UC), and Crohn's disease (CD), as well some new experimental compounds with PPAR activity as promising drugs for IBD treatment. Yes
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- 2020
6. Energy sensors in drug addiction: A potential therapeutic target.
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López‐Gambero, Antonio Jesús, Rodríguez de Fonseca, Fernando, Suárez, Juan, and López-Gambero, Antonio Jesús
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DRUG addiction , *SCIENTIFIC literature , *REWARD (Psychology) , *NUCLEUS accumbens , *NEUROPLASTICITY , *RESEARCH funding - Abstract
Addiction is defined as the repeated exposure and compulsive seek of psychotropic drugs that, despite the harmful effects, generate relapse after the abstinence period. The psychophysiological processes associated with drug addiction (acquisition/expression, withdrawal, and relapse) imply important alterations in neurotransmission and changes in presynaptic and postsynaptic plasticity and cellular structure (neuroadaptations) in neurons of the reward circuits (dopaminergic neuronal activity) and other corticolimbic regions. These neuroadaptation mechanisms imply important changes in neuronal energy balance and protein synthesis machinery. Scientific literature links drug-induced stimulation of dopaminergic and glutamatergic pathways along with presence of neurotrophic factors with alterations in synaptic plasticity and membrane excitability driven by metabolic sensors. Here, we provide current knowledge of the role of molecular targets that constitute true metabolic/energy sensors such as AMPK, mTOR, ERK, or KATP in the development of the different phases of addiction standing out the main brain regions (ventral tegmental area, nucleus accumbens, hippocampus, and amygdala) constituting the hubs in the development of addiction. Because the available treatments show very limited effectiveness, evaluating the drug efficacy of AMPK and mTOR specific modulators opens up the possibility of testing novel pharmacotherapies for an individualized approach in drug abuse. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Energy sensors in drug addiction: A potential therapeutic target
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López‐Gambero, Antonio Jesús, primary, Rodríguez de Fonseca, Fernando, additional, and Suárez, Juan, additional
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- 2020
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8. Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases
- Author
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Decara, Juan, primary, Rivera, Patricia, additional, López-Gambero, Antonio Jesús, additional, Serrano, Antonia, additional, Pavón, Francisco Javier, additional, Baixeras, Elena, additional, Rodríguez de Fonseca, Fernando, additional, and Suárez, Juan, additional
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- 2020
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9. Differential hepatoprotective role of the cannabinoid CB 1 and CB 2 receptors in paracetamol‐induced liver injury
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Rivera, Patricia, primary, Vargas, Antonio, additional, Pastor, Antoni, additional, Boronat, Anna, additional, López‐Gambero, Antonio Jesús, additional, Sánchez‐Marín, Laura, additional, Medina‐Vera, Dina, additional, Serrano, Antonia, additional, Pavón, Francisco Javier, additional, Torre, Rafael, additional, Agirregoitia, Ekaitz, additional, Lucena, María Isabel, additional, Rodríguez de Fonseca, Fernando, additional, Decara, Juan, additional, and Suárez, Juan, additional
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- 2020
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10. Epicardial cell lineages and the origin of the coronary endothelium
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Carmona, Rita, primary, Barrena, Silvia, additional, López Gambero, Antonio Jesús, additional, Rojas, Anabel, additional, and Muñoz‐Chápuli, Ramón, additional
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- 2020
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11. Differential hepatoprotective role of the cannabinoid CB1 and CB2 receptors in paracetamol-induced liver injury.
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Rivera, Patricia, Vargas, Antonio, Pastor, Antoni, Boronat, Anna, López‐Gambero, Antonio Jesús, Sánchez‐Marín, Laura, Medina‐Vera, Dina, Serrano, Antonia, Pavón, Francisco Javier, Torre, Rafael, Agirregoitia, Ekaitz, Lucena, María Isabel, Rodríguez de Fonseca, Fernando, Decara, Juan, Suárez, Juan, López-Gambero, Antonio Jesús, Sánchez-Marín, Laura, Medina-Vera, Dina, and de la Torre, Rafael
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CANNABINOID receptors ,LIVER injuries ,HEPATITIS ,ACETAMINOPHEN ,HEPATOTOXICOLOGY - Abstract
Background and Purpose: Protective mechanisms of the endogenous cannabinoid system against drug-induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation.Experimental Approach: The 2-arachidonoylglycerol (2-AG)-related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg-1 ·day-1 ) of paracetamol (acetaminophen), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg·kg-1 ), or lacking CB1 and CB2 receptors.Key Results: Acute paracetamol increased the expression of CB2 , ABHD6 and COX-2, while repeated paracetamol increased that of CB1 and COX-2 and decreased that of DAGLβ. Both acute paracetamol and repeated paracetamol decreased the liver content of acylglycerols (2-AG, 2-LG and 2-OG). Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute paracetamol-exposed CB2 KO mice had higher expression of the fibrogenic αSMA and the cytokine IL-6 and lower apoptotic cleaved caspase 3. CB1 deficiency enhanced the repeated APAP-induced increases in αSMA and cleaved caspase 3 and blocked those of CYP2E1, TNF-α, the chemokine CCL2 and the circulating γ-glutamyltransferase (γGT). Although JWH015 reduced the expression of αSMA and TNF-α in acute paracetamol, ACEA increased the expression of cleaved caspase 3 and CCL2 in repeated paracetamol.Conclusion and Implications: The differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to paracetamol-induced hepatotoxicity should be considered for designing alternative therapies against DILI. [ABSTRACT FROM AUTHOR]- Published
- 2020
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12. Three embryonic cell lineages related with the epicardium show distinct developmental fates
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Carmona, Rita, Ariza, Laura, López Gambero, Antonio Jesús, Pérez Pomares, José María, and Muñoz-Chápuli, Ramón
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linaje celular ,Sistema Cardiovascular ,cardiovascular system ,Epicardio ,WT1 - Abstract
The embryonic epicardium generates a population of mesenchymal cells that contribute to the coronary vessels and the connective tissue of the adult heart. We have used murine cell-tracing models to compare the developmental fate of three different lineages related with the epicardium. Mice bearing R26R-EYFP reporters were crossed with mice expressing Cre-recombinase under control of the promoters of the cardiac troponin gene (cTnT), the Wilms tumor suppressor gene (Wt1), and the G2 enhancer of the GATA4 gene. Thus, we could trace, using confocal microscopy and flow cytometry, the lineage of the cardiac cells expressing Wt1, cTnT and GATA4 under control of the G2 enhancer, from midgestation to adults. Additionally we have studied a knockin Wt1-GFP reporter model to detect cells with Wt1 expression in the developing and adult heart. During development, Wt1 is expressed in a major part of the proepicardium and epicardium, and also in some epicardial-derived mesenchymal cells, in part of the mesenchymal and coronary endothelial cells and also in a fraction of the cardiomyocytes. GATA4 expression is activated by the enhancer G2 in lateral mesoderm and pro/epicardium, but not in epicardial-derived cells, although most of these cells as well as some cardiomyocytes originate from a G2-GATA4 expressing lineage. cTnT is expressed in all the cardiomyocytes, but a part of the epicardial cells also derives from a cTnTCre-EYFP positive cell lineage. The developmental fate of these linages reveals interesting differences, according to our preliminary results. For example, the G2-GATA4 cell linage contributes more than the Wt1 cell lineage to the coronary endothelium during development. However, both lineages are highly represented in the adult cardiac endothelium, suggesting postnatal expression of Wt1 in the coronary endothelium and incorporation of endothelial progenitor cells from bone marrow (where the G2-GATA4 reporter is active in 20% of hematopoietic stem cells). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
- Published
- 2018
13. d-Pinitol promotes tau dephosphorylation through a cyclin-dependent kinase 5 regulation mechanism: A new potential approach for tauopathies?
- Author
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Dina Medina‐Vera, Juan Antonio Navarro, Patricia Rivera, Cristina Rosell‐Valle, Alfonso Gutiérrez‐Adán, Carlos Sanjuan, Antonio Jesús López‐Gambero, Rubén Tovar, Juan Suárez, Francisco Javier Pavón, Elena Baixeras, Juan Decara, Fernando Rodríguez de Fonseca, European Commission, Ministerio de Economía, Industria y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Ministerio de Sanidad (España), Medina-Vera, Dina, Navarro, Juan Antonio, Rivera, Patricia, Rosell-Valle, Cristina, Gutiérrez-Adán, Alfonso, López-Gambero, Antonio Jesús, Suárez, Juan, Pavón, Francisco Javier, Baixeras, Elena, Decara, Juan, Rodríguez de Fonseca, Fernando, Medina-Vera, Dina [0000-0002-0342-1287], Navarro, Juan Antonio [0000-0003-3089-0983], Rivera, Patricia [0000-0002-0478-6667], Rosell-Valle, Cristina [0000-0001-9545-0976], Gutiérrez-Adán, Alfonso [0000-0001-9893-9179], López-Gambero, Antonio Jesús [0000-0001-7716-9056], Suárez, Juan [0000-0001-5254-9802], Pavón, Francisco Javier [0000-0002-5256-8904], Baixeras, Elena [0000-0001-6955-2434], Decara, Juan [0000-0002-9868-015X], and Rodríguez de Fonseca, Fernando [0000-0002-4516-5795]
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Pharmacology ,Leptin ,d-pinitol ,Akt ,CDK5 ,Insulins ,Cyclin-Dependent Kinase 5 ,tau Proteins ,Tau phosphorylation ,Rats ,Rats, Zucker ,Glycogen Synthase Kinase 3 ,Mice ,Tauopathy ,Tauopathies ,Animals ,Insulin ,Phosphorylation ,Rats, Wistar ,Inositol - Abstract
18 Pág. Departamento de Reproducción animal., Recent evidence links brain insulin resistance with neurodegenerative diseases, where hyperphosphorylated tau protein contributes to neuronal cell death. In the present study, we aimed to evaluate if d-pinitol inositol, which acts as an insulin sensitizer, affects the phosphorylation status of tau protein., This research was funded by the European Regional Development Funds-European Union (ERDF-EU), FATZHEIMER project (EU-LAC HEALTH 2020, 16/T010131), “Una manera de hacer Europa”; Ministerio de Economía, Industria y Competitividad, Gobierno de España, Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (RTC-2016-4983-1); ERDF-EU-Instituto de Salud Carlos III (ISCIII), Proyectos de investigación en salud (PI19/01577); Consejería de Salud y Familias, Junta de Andalucía, Proyecto de Investigación en Salud (PI-0139-2018); Consejería de Economía, Conocimiento y Universidad, Junta de Andalucía, Plan Andaluz de Investigación, Desarrollo e Innovación (P18-TP-5194); Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Salud, Gobierno de España (PND2020/048). D.M-V. (FI20/00227) holds a “PFIS” predoctoral contract from the National System of Health, ERDF-EU-Instituto de Salud Carlos III. A.J.L.-G. (IFI18/00042) holds an “iPFIS” predoctoral contract from the National System of Health, ERDF-EU-ISCIII. P.R. (CP19/00068), F.J.P. (CPII19/00022) and J.D. (CP21/00021) hold a “Miguel Servet” research contract from the National System of Health, ISCIII co-funded by European Social Fund, “Investing in your future,” Gobierno de España.
- Published
- 2022
14. Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance.
- Author
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Medina-Vera D, López-Gambero AJ, Navarro JA, Sanjuan C, Baixeras E, Decara J, and de Fonseca FR
- Abstract
Alzheimer's disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer's disease. The pathogenesis of Alzheimer's disease is mainly mediated by the phosphorylation and aggregation of tau protein. Among the multiple causes of tau hyperphosphorylation, brain insulin resistance has generated much attention, and inositols as insulin sensitizers, are currently considered candidates for drug development. The present narrative review revises the interactions between these three elements: Alzheimer's disease-tau-inositols, which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease., Competing Interests: None
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- 2024
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