Publications by authors named "E Ortega Izquierdo"

143 Publications

Click and count: specific detection of acid ceramidase activity in live cells.

Chem Sci 2020 Oct 22;11(48):13044-13051. Epub 2020 Oct 22.

Research Unit on BioActive Molecules, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) Jordi Girona 18 08034-Barcelona Spain

The use of intact cells in medical research offers a number of advantages over employing cell-free systems. In diagnostics, cells isolated from liquid biopsies can be directly used, speeding up the time of analysis and diminishing the risk of protein degradation by sample manipulation. In drug discovery, studies in live cells take into account aspects neglected in cell-free systems, such as uptake, metabolization, and subcellular concentration by compartmentalization of potential drug candidates. Therefore, probes for studies are of paramount importance. Acid ceramidase (AC) is a lysosomal enzyme that hydrolyses ceramides into sphingoid bases and fatty acids. The essential role of this enzyme in the outburst and progress of several diseases, some of them still incurable, is well sustained. Despite the great clinical relevance of AC as a biomarker and therapeutic target, the specific monitoring of AC activity in live cells has remained elusive due to the concomitant existence of neutral and alkaline ceramidases. In this work, we report that 1-deoxydihydroceramides are exclusively hydrolysed by AC. Using -octanoyl-18-azidodeoxysphinganine as a probe and a BODIPY-substituted bicyclononyne, we show the click-reliant predominant staining of lysosomes, with extra-lysosomal labeling also occurring in some cells. Importantly, using pharmacological and genetic tools together with high resolution mass spectrometry, we demonstrate that both lysosomal and extra-lysosomal staining are AC-dependent. These findings are translated into the specific flow cytometry monitoring of AC activity in intact cells, which fills an important gap in the field of diseases linked to altered AC activity.
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http://dx.doi.org/10.1039/d0sc03166fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163297PMC
October 2020

Oral Mucosa as a Potential Site for Diagnosis and Treatment of Allergic and Autoimmune Diseases.

Foods 2021 Apr 28;10(5). Epub 2021 Apr 28.

Institute of Applied Molecular Medicine, Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, 28003 Madrid, Spain.

Most prevalent food allergies during early childhood are caused by foods with a high allergenic protein content, such as milk, egg, nuts, or fish. In older subjects, some respiratory allergies progressively lead to food-induced allergic reactions, which can be severe, such as urticaria or asthma. Oral mucosa remodeling has been recently proven to be a feature of severe allergic phenotypes and autoimmune diseases. This remodeling process includes epithelial barrier disruption and the release of inflammatory signals. Although little is known about the immune processes taking place in the oral mucosa, there are a few reports describing the oral mucosa-associated immune system. In this review, we will provide an overview of the recent knowledge about the role of the oral mucosa in food-induced allergic reactions, as well as in severe respiratory allergies or food-induced autoimmune diseases, such as celiac disease.
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http://dx.doi.org/10.3390/foods10050970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146604PMC
April 2021

Novel biallelic variant in BBS9 causative of Bardet-Biedl syndrome: expanding the spectrum of disease-causing genetic alterations.

BMC Med Genomics 2021 03 26;14(1):91. Epub 2021 Mar 26.

Genomics Unit, Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM), C/Doctor Esquerdo 46, 28007, Madrid, Spain.

Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy disorder. Many BBS disease-causing genetic variants have been identified due to the advancement of molecular diagnostic tools. We report on a novel pathogenic variant in a consanguineous Pakistani family with an affected child.

Case Presentation: Clinical exome sequencing was used to search for BBS causing variants in the affected individual and identified a novel homozygous splice-site variant in the BBS9 gene (c.702 + 1del). Sanger sequencing was performed for variant validation and segregation studies. Expression analysis using mRNA levels to assess the functional impact of the novel variant demonstrated skipping of exon 7 in the affected alleles, suggesting a truncating effect. Three-dimensional structural modelling was used to predict pathogenicity of the variant residue and the alteration leads to a partial deletion of the PHTB1_N domain and a total deletion of the PHTB1_C domain.

Conclusion: The study of this case expands the spectrum of biallelic variants in the BBS9 gene associated with BBS and increased the knowledge on the molecular consequences of splicing variation c.702 + 1del.
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http://dx.doi.org/10.1186/s12920-021-00943-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995718PMC
March 2021

Herpes simplex virus 1 proteins can induce skin inflammation in an atopic dermatitis-like mouse model.

Exp Dermatol 2021 Mar 22. Epub 2021 Mar 22.

Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.

Herpes simplex virus type 1 (HSV-1) can induce in certain individuals with atopic dermatitis (AD) severe cutaneous infections that can spread throughout the entire body, a condition named as AD complicated by eczema herpeticum (ADEH). It has been recently found that ADEH patients can produce specific IgE against HSV-1 proteins, which may contribute to lower protection against HSV-1. However, little is known about the capacity of these HSV-1 proteins to produce an inflammatory response at the skin level. In this study, using a mouse model of AD-like dermatitis, three HSV-1 proteins (glycoprotein D -gD-, glycoprotein B -gB- and VP22) were applied on tape-stripped back skin mice in three exposures periods. Ovalbumin (OVA) and 0.9% NaCl were used as positive and negative controls, respectively. Skin samples were obtained for analysis of specific cell components of skin infiltration. The results showed that the viral protein gD induced a statistically significant increase in the number of dermal infiltrating CD3+, CD4+ cells and mast cells compared with the negative control group. gD was also able to induce epidermal thickening and epidermal infiltration of T cells closely related to the one produced in mice sensitized with OVA. However, VP22 and gB contributed to a lesser extent to skin inflammation. These results showed that proteins from HSV-1, especially gD, can have per se an important T cell and mast cell-driven inflammatory potential at the skin level.
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http://dx.doi.org/10.1111/exd.14327DOI Listing
March 2021

A Neuromechanical Model of Multiple Network Rhythmic Pattern Generators for Forward Locomotion in .

Front Comput Neurosci 2021 18;15:572339. Epub 2021 Feb 18.

Cognitive Science Program, Indiana University Bloomington, Bloomington, IN, United States.

Multiple mechanisms contribute to the generation, propagation, and coordination of the rhythmic patterns necessary for locomotion in . Current experiments have focused on two possibilities: pacemaker neurons and stretch-receptor feedback. Here, we focus on whether it is possible that a chain of multiple network rhythmic pattern generators in the ventral nerve cord also contribute to locomotion. We use a simulation model to search for parameters of the anatomically constrained ventral nerve cord circuit that, when embodied and situated, can drive forward locomotion on agar, in the absence of pacemaker neurons or stretch-receptor feedback. Systematic exploration of the space of possible solutions reveals that there are multiple configurations that result in locomotion that is consistent with certain aspects of the kinematics of worm locomotion on agar. Analysis of the best solutions reveals that gap junctions between different classes of motorneurons in the ventral nerve cord can play key roles in coordinating the multiple rhythmic pattern generators.
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http://dx.doi.org/10.3389/fncom.2021.572339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930337PMC
February 2021