5 results on '"Ainara Vallejo-Illarramendi"'
Search Results
2. Discovery of a novel family of FKBP12 'reshapers' and their use as calcium modulators in skeletal muscle under nitro-oxidative stress
- Author
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Garazi Aldanondo, Maite Eceiza, José I. Miranda, Ainara Vallejo-Illarramendi, Maialen Sagartzazu-Aizpurua, Pablo Marco-Moreno, Aitziber Irastorza, Pablo Ferrón, Jesus M. Aizpurua, Adolfo López de Munain, Haizpea Lasa-Fernández, Endika Torres, and Naroa Dadie
- Subjects
chemistry.chemical_element ,Tacrolimus Binding Protein 1A ,Calcium ,Muscle disorder ,01 natural sciences ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Humans ,Muscle, Skeletal ,030304 developmental biology ,Pharmacology ,RYR1 ,0303 health sciences ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Ryanodine receptor ,Myogenesis ,Calcium channel ,Organic Chemistry ,Skeletal muscle ,Ryanodine Receptor Calcium Release Channel ,General Medicine ,Triazoles ,0104 chemical sciences ,Cell biology ,Oxidative Stress ,HEK293 Cells ,medicine.anatomical_structure ,chemistry ,Peroxynitrite - Abstract
The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through molecular “reshaping” of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC “click” protocols amenable to one-pot transformations in high overall yields and total configurational integrity. To model nitro-oxidative stress, human myotubes were treated with the peroxynitrite donor SIN1, and evidence was found that some triazoles 10 were able to normalize calcium levels, as well as FKBP12/RyR1 interaction. For example, compound 10 b at 150 nM rescued 46% of FKBP12/RyR1 interaction and up to 70% of resting cytosolic calcium levels in human myotubes under nitro-oxidative stress. All compounds 10 analyzed showed target engagement to FKBP12 and low levels of cytotoxicity in vitro. Compounds 10b, 10c, 10h, and 10iR were identified as potential therapeutic candidates to protect myotubes in muscle disorders with underlying nitro-oxidative stress, FKBP12/RyR1 dysfunction and calcium dysregulation.
- Published
- 2021
3. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage
- Author
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David Otaegui, Ander Matheu, Haizea Iribar, Izaskun Burgoa, Virginia Pérez-López, Mario García-Domínguez, Maria Paz Lopez-Mato, Araika Gutiérrez-Rivera, Olatz Leis, Ariane Aduriz, Angel G. Martin, Ander Izeta, Haritz Irizar, Maider Muñoz-Culla, Nuria Gago-Lopez, Adrián Pérez-San Vicente, Robb MacLellan, Usue Etxaniz, Ainara Vallejo-Illarramendi, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Eusko Jaurlaritza, and European Commission
- Subjects
Adult ,Male ,Lineage (genetic) ,Adolescent ,Cell ,Foreskin ,Nerve Tissue Proteins ,Receptors, Nerve Growth Factor ,Biology ,Biochemistry ,Article ,Transcriptome ,Mice ,Young Adult ,SOX2 ,Dermis ,Neural Stem Cells ,Precursor cell ,Genetics ,medicine ,Animals ,Humans ,Cell Lineage ,Child ,lcsh:QH301-705.5 ,Cells, Cultured ,Aged ,Neurons ,lcsh:R5-920 ,Microscopy, Confocal ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Infant ,Cell Differentiation ,Cell Biology ,Middle Aged ,CD56 Antigen ,Cell biology ,stomatognathic diseases ,medicine.anatomical_structure ,lcsh:Biology (General) ,Child, Preschool ,Immunology ,Neural differentiation ,Schwann Cells ,lcsh:Medicine (General) ,Developmental Biology - Abstract
Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread., Graphical Abstract, Highlights • Human dermis-derived cultures show two types of SOX2+ cells: Schwann and perivascular • p75NTR+CD56+ Schwann cells are responsible for neural progeny • SOX2 expression levels regulate the neural competence of dermal precursors • p75NTR+CD56+ neural precursor cells similarly arise from human cardiospheres, In this article, Izeta and colleagues show that neural precursor cell (NPC) cultures from adult human dermis include two SOX2+ cell subpopulations (Schwann and perivascular), and neural progeny is derived only from Schwann cells in a process regulated by their SOX2 expression levels. NPCs similarly arise from human cardiospheres, potentially elucidating the origin of seemingly unrelated NPCs observed in multiple organs.
- Published
- 2014
- Full Text
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4. Deletion of Integrin-Linked Kinase from Skeletal Muscles of Mice Resembles Muscular Dystrophy Due to α7β1-Integrin Deficiency
- Author
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Keling Zang, Ania L. Gheyara, René St.-Arnaud, Lin Mei, Shoukat Dedhar, Louis F. Reichardt, and Ainara Vallejo-Illarramendi
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Integrins ,macromolecular substances ,Protein Serine-Threonine Kinases ,Muscular Dystrophies ,Pathology and Forensic Medicine ,Focal adhesion ,Mice ,medicine ,Animals ,Integrin-linked kinase ,Muscular dystrophy ,Muscle, Skeletal ,Paxillin ,Mice, Knockout ,Focal Adhesions ,biology ,Vinculin ,medicine.disease ,Actin cytoskeleton ,Cell biology ,Biochemistry ,Mutation ,embryonic structures ,biology.protein ,Dystrophin ,ITGA7 ,Regular Articles - Abstract
Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein that links integrins to the actin cytoskeleton and to a number of signaling pathways involved in integrin action. We hypothesized that Ilk may act as an important effector of integrins in skeletal muscle, where these receptors provide a critical link between the sarcolemma and the extracellular matrix. Using the cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting mutants developed a progressive muscular dystrophy with multiple degenerating and regenerating muscle fibers, increased central nuclei, and endomysial fibrosis. These defects were widespread but were most severe near myofascial junctions where Ilk mutants showed displacement of focal adhesion-related proteins, including vinculin, paxillin, focal adhesion kinase, dystrophin, and the alpha 7 beta 1D-integrin subunits. Distal ends of mutant muscle fibers appeared irregular, and there was restructuring of the actin cytoskeleton. These findings resemble those seen in humans and mice lacking the alpha 7-integrin subunit and suggest that Ilk may act as a cytoplasmic effector of alpha 7 beta1-integrin in the pathogenesis of these deficiencies.
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- 2007
5. Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients
- Author
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Gixane González-García, Aitor Palomino, Carlos Matute, Ainara Vallejo-Illarramendi, Ana González-Pinto, Cristina González-Gómez, A. Aldama, and Fernando Mosquera
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Pediatrics ,medicine.medical_specialty ,business.industry ,Follow up studies ,Case-control study ,MEDLINE ,Retrospective cohort study ,medicine.disease ,First episode schizophrenia ,Psychiatry and Mental health ,Text mining ,medicine ,Analysis of variance ,Bipolar disorder ,business ,Biological Psychiatry - Published
- 2006
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