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Your search keyword '"Hernandez-Alcoceba R"' showing total 4 results
Start Over Author "Hernandez-Alcoceba R" Publisher elsevier
4 results on '"Hernandez-Alcoceba R"'

1. Proteomic analysis of human hepatoma cells expressing methionine adenosyltransferase I/III Characterization of DDX3X as a target of S-adenosylmethionine

Author

Schröder, P.C. (Paul C.), Fernandez-Irigoyen, J. (Joaquín), Bigaud, E. (Emilie), Serna, A. (Antonio), Hernandez-Alcoceba, R. (Rubén), Lu, S.C. (Shelly C.), Mato, J.M. (José María), Prieto, J. (Jesús), and Corrales, F.J. (Fernando José)

Subjects
Proteomics, S-adenosylmethionine, Mass spectrometry, Hepatocellular carcinoma, DDX3X, 2D-DIGE
Abstract

Methionine adenosyltransferase I/III (MATI/III) synthesizes S-adenosylmethionine (SAM) in quiescent hepatocytes. Its activity is compromised in most liver diseases including liver cancer. Since SAM is a driver of hepatocytes fate we have studied the effect of re-expressing MAT1A in hepatoma Huh7 cells using proteomics. MAT1A expression leads to SAM levels close to those found in quiescent hepatocytes and induced apoptosis. Normalization of intracellular SAM induced alteration of 128 proteins identified by 2D-DIGE and gel-free methods, accounting for deregulation of central cellular functions including apoptosis, cell proliferation and survival. Human Dead-box protein 3 (DDX3X), a RNA helicase regulating RNA splicing, export, transcription and translation was down-regulated upon MAT1A expression. Our data support the regulation of DDX3X levels by SAM in a concentration and time dependent manner. Consistently, DDX3X arises as a primary target of SAM and a principal intermediate of its antitumoral effect. Based on the parallelism between SAM and DDX3X along the progression of liver disorders, and the results reported here, it is tempting to suggest that reduced SAM in the liver may lead to DDX3X up-regulation contributing to the pathogenic process and that replenishment of SAM might prove to have beneficial effects, at least in part by reducing DDX3X levels. This article is part of a Special Issue entitled: Clinical Proteomics.

Published
2012

2. Inhibition of adenovirus infection by mifepristone.

Author

Marrugal-Lorenzo JA, Serna-Gallego A, González-González L, Buñuales M, Poutou J, Pachón J, Gonzalez-Aparicio M, Hernandez-Alcoceba R, and Sánchez-Céspedes J

Subjects
A549 Cells, Animals, Female, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Adenoviridae Infections drug therapy, Adenoviruses, Human drug effects, Antiviral Agents therapeutic use, Drug Repositioning, Mifepristone therapeutic use
Abstract

The repurposing of drugs approved by the regulatory agencies for other indications is emerging as a valuable alternative for the development of new antimicrobial therapies, involving lower risks and costs than the de novo development of novel antimicrobial drugs. Adenovirus infections have showed a steady increment in recent years, with a high clinical impact in both immunosuppressed and immunocompetent patients. In this context, the lack of a specific drug to treat these infections supports the search for new therapeutic alternatives. In this study, we examined the anti-HAdV properties of mifepristone, a commercially available synthetic steroid drug. Mifepristone showed significant in vitro anti-HAdV activity at low micromolar concentrations with little cytotoxicity. Our mechanistic assays suggest that this drug could affect the microtubule transport, interfering with the entry of the virus into the nucleus and therefore inhibiting HAdV infection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
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3. Visualization of the therapeutic efficacy of a gene correction approach in Wilson's disease by laser-ablation inductively coupled mass spectrometry.

Author

Moreno D, Murillo O, Gazquez C, Hernandez-Alcoceba R, Uerlings R, Gonzalez-Aseguinolaza G, and Weiskirchen R

Subjects
Animals, Copper metabolism, Copper-Transporting ATPases deficiency, Copper-Transporting ATPases genetics, Copper-Transporting ATPases metabolism, Dependovirus genetics, Hepatolenticular Degeneration metabolism, Humans, Liver metabolism, Male, Mass Spectrometry methods, Mice, Mice, Knockout, Hepatolenticular Degeneration genetics, Hepatolenticular Degeneration therapy, Targeted Gene Repair methods
Published
2018
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4. Long-term metabolic correction of Wilson's disease in a murine model by gene therapy.

Author

Murillo O, Luqui DM, Gazquez C, Martinez-Espartosa D, Navarro-Blasco I, Monreal JI, Guembe L, Moreno-Cermeño A, Corrales FJ, Prieto J, Hernandez-Alcoceba R, and Gonzalez-Aseguinolaza G

Subjects
Adenosine Triphosphatases genetics, Animals, Cation Transport Proteins genetics, Copper-Transporting ATPases, Disease Models, Animal, Disease Progression, Gene Transfer Techniques, Humans, Mice, Peptide Fragments genetics, Treatment Outcome, alpha 1-Antitrypsin genetics, Copper metabolism, Genetic Therapy methods, Genetic Vectors administration & dosage, Hepatolenticular Degeneration genetics, Hepatolenticular Degeneration metabolism, Hepatolenticular Degeneration therapy, Liver metabolism, Liver pathology
Abstract

Background & Aims: Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in the ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In this work we assessed the efficacy of gene therapy to treat this condition., Methods: We transduced the liver of the Atp7b(-/-) WD mouse model with an adeno-associated vector serotype 8 (AAV8) encoding the human ATP7B cDNA placed under the control of the liver-specific α1-antitrypsin promoter (AAV8-AAT-ATP7B). After vector administration we carried out periodic evaluation of parameters associated with copper metabolism and disease progression. The animals were sacrificed 6months after treatment to analyze copper storage and hepatic histology., Results: We observed a dose-dependent therapeutic effect of AAV8-AAT-ATP7B manifested by the reduction of serum transaminases and urinary copper excretion, normalization of serum holoceruloplasmin, and restoration of physiological biliary copper excretion in response to copper overload. The liver of treated animals showed normalization of copper content and absence of histological alterations., Conclusions: Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2016
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