Isabel Fabregat

Institut d'Investigació Biomédica de Bellvitge

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Esther Bertrán

Institut d'Investigació Biomédica de Bellvitge

Aránzazu Sánchez

Universidad Complutense de Madrid

Blanca Herrera

Hospital Clínico San Carlos

Cesáreo Roncero

Universidad Complutense de Madrid

Patricia Sancho

Hospital Universitario Miguel Servet

Manuel Benito

Universidad Complutense de Madrid

Laia Caja

Science for Life Laboratory

Margarita Fernández

Pennsylvania State University

Gianluigi Giannelli

Gastroenterology Hospital "Saverio de Bellis"

AÁ

Alberto Álvarez

Universidad de Extremadura

Cooperative Institutions

Instituto de Salud Carlos III

173

Universitat de Barcelona

168

Centro de Investigación Biomédica en Red

144

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

131

Inserm

100

Institut d'Investigació Biomédica de Bellvitge

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Consejo Superior de Investigaciones Científicas

Universidad Autónoma de Madrid

Centre for Biomedical Network Research on Rare Diseases

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Senescence, hand in hand with hepatic iron overload during the progression of NAFLD

Journal of Hepatology (2022)

Miren Bravo Jorge Simón Naroa Goikoetxea Sofía Lachiondo‐Ortega Leire Egia‐Mendikute

Senescence

10.1016/s0168-8278(22)01664-6

Cite

Citations (0)

Glucocorticoid receptor down-Regulates c-jun amino terminal kinases induced by tumor necrosis factor ? in fetal rat hepatocyte primary cultures

Hepatology (1999)

Juan‐José Ventura Cesáreo Roncero Isabel Fabregat Manuel Benito

The effect of dexamethasone on Jun N–terminal kinase (JNK) activity was assayed by using fetal hepatocytes in primary culture. The addition of tumor necrosis factor α (TNF–α) caused an increase in JNK in a dose– and time–dependent manner. We show that activation of JNK by this extracellular signal is inhibited by dexamethasone in a dose–dependent fashion. This inhibitory effect was observed in cells treated for 10 minutes with dexamethasone in the presence of protein phosphatase inhibitors such as orthovanadate or okadaic acid, or in cells previously treated with actinomycin D. Glucocorticoid receptor (GR) can be precipitated with the fusion protein, GST-c–Jun (1–79), bound to agarose beads. However, the inhibitory effect of glucocorticoids on JNK activity was also observed using ATF–2 as substrate. In addition, dexamethasone inhibits JNK phosphorylation induced by TNF–α. Finally, we show that GR can also be phosphorylated in tyrosine residues in response to TNF–α and epidermal growth factor (EGF) upon ligand–binding. Our results suggest that the anti–inflammatory effect of glucocorticoids on the inflammatory pathways induced by TNF–α can be explained, at least in part, by modulating JNK activity through a direct protein–protein interaction; the JNK phosphorylation and tyrosine–phosphorylation state of GR may be regulatory steps also involved in that effect.

10.1002/hep.510290339

Cite

Citations (23)

Possible involvement of NADPH requirement in regulation of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase levels in rat liver

Molecular and Cellular Biochemistry (1990)

Antonio Ayala Isabel Fabregat Alberto Machado

Glucose 6-phosphate

10.1007/bf00219968

Cite

Citations (8)

CCDC 964851: Experimental Crystal Structure Determination

The Cambridge Structural Database (2014)

Alba Pérez‐Perarnau Sara Preciado Claudia Mariela Palmeri Cristina Moncunill‐Massaguer Daniel Iglesias‐Serret

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Crystal (programming language)

10.5517/cc11d07p

Cite

Citations (0)

Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR

Frontiers in Immunology (2021)

Marta Compte Seandean L. Harwood Jorge L. Martínez‐Torrecuadrada Gema Pérez-Chacón Patricia González‐García

Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BB-agonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcγR interactions in the major off-tumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemic cancer immunotherapy protocols.

Agonistic behaviour

10.3389/fimmu.2020.614363

Cite

Citations (8)

Snail: in the cross-roads among EMT and apoptosis

Jèssica Mainez Diana L. Franco Sonia Vega Patricia Sancho Miguel Murillo

Source

Cite

Citations (0)

The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-β-induced apoptosis of liver tumor cells

Biochemical Pharmacology (2011)

Patricia Sancho Isabel Fabregat

NOX1

10.1016/j.bcp.2011.01.007

Cite

Citations (46)

Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor β in rat fetal hepatocytes

Hepatology (2001)

Blanca Herrera Margarita Fernández Alberto Álvarez Cesáreo Roncero Manuel Benito

Most of the morphologic changes that are observed in apoptotic cells are caused by a set of cysteine proteases (caspases) that are activated during this process. In previous works from our group we found that treatment of rat fetal hepatocytes with transforming growth factor β1 (TGF-β1) is followed by apoptotic cell death. TGF-β1 mediates radical oxygen species (ROS) production that precedes bcl-x L down-regulation, loss of mitochondrial transmembrane potential, release of cytochrome c, and activation of caspase-3 (Herrera et al., FASEB J 2001;15:741-751). In this work, we have analyzed how TGF-β1 activates the caspase cascade and whether or not caspase activation precedes the oxidative stress induced by this factor. Our results show that TGF-β1 activates at least caspase-3, -8, and -9 in rat fetal hepatocytes, which are not required for ROS production, glutathione depletion, bcl-x L down-regulation, and initial cytochrome c release. However, caspase activation mediates cleavage of Bid and Bcl-x L that could originate an amplification loop on the mitochondrial events. An interesting result is that transmembrane potential disruption occurs later than the initial cytochrome c release and is mostly blocked by the pan-caspase inhibitor Z-VAD.fmk, indicating that the decrease in mitochondrial transmembrane potential (ΔΨm) may be a consequence of caspase activity rather than the mechanism by which TGF-β induces cytochrome c efflux. Finally, although Z-VAD.fmk completely blocks nucleosomal DNA fragmentation, it only delays cell death, which suggests that activation of the apoptotic program by TGF-β in fetal hepatocytes inevitably leads to death, with or without caspases. (Hepatology 2001;34:548-556.)

Bcl-xL

10.1053/jhep.2001.27447

Cite

Citations (118)

AISF position paper on liver transplantation and pregnancy

Digestive and Liver Disease (2016)

Anna Alisi Clara Balsano Veronica Bernabucci Annalisa Berzigotti Maurizia Rossana Brunetto

Liver function

10.1016/j.dld.2016.04.009

Cite

Citations (23)

A novel role for BMP9 as a negative regulator of oval cell-mediated regeneration in response to liver damage