A5016383461- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Redox biology and oxidative stress
- Genetics and Neurodevelopmental Disorders
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Metabolism and Genetic Disorders
- Alzheimer's disease research and treatments
- ATP Synthase and ATPases Research
- Genetic Neurodegenerative Diseases
- Genomics, phytochemicals, and oxidative stress
- Ion channel regulation and function
- Glutathione Transferases and Polymorphisms
- Cannabis and Cannabinoid Research
- Sirtuins and Resveratrol in Medicine
- Neuropeptides and Animal Physiology
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- Genetics, Aging, and Longevity in Model Organisms
- Peptidase Inhibition and Analysis
- Renal and related cancers
- FOXO transcription factor regulation
- Anesthesia and Neurotoxicity Research
- Diet, Metabolism, and Disease
- RNA regulation and disease
Universitat de Barcelona
2012-2024
University of Edinburgh
2006-2016
Faculty (United Kingdom)
2015
Institute for Research in Biomedicine
2006-2012
Hospital Universitario Fundación Jiménez Díaz
2006
Mario Negri Institute for Pharmacological Research
2003
Hospital Universitario Ramón y Cajal
1981-1995
Centro de Ingeniería Genética y Biotecnología
1995
In many cells and specially in muscle, mitochondria form elongated filaments or a branched reticulum. We show that Mfn2 (mitofusin 2), mitochondrial membrane protein participates fusion mammalian cells, is induced during myogenesis contributes to the maintenance operation of network. Repression caused morphological functional fragmentation network into independent clusters. Concomitantly, repression reduced glucose oxidation, potential, cell respiration, proton leak. also Mfn2-dependent...
The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates the maintenance of network and regulates metabolism intracellular signaling. potential for regulation human expression vivo largely unknown. Based on presence dysfunction insulin-resistant conditions, we have examined whether dysregulated skeletal muscle from obese or nonobese 2 diabetic subjects, regulated by body weight loss, regulatory role tumor necrosis...
Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that participates in fusion and regulates metabolism mammalian cells. Here, we show Mfn2 gene expression induced skeletal muscle brown adipose tissue by conditions associated with enhanced energy expenditure, such as cold exposure or beta(3)-adrenergic agonist treatment. In keeping the role of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha on demonstrate stimulatory effect PGC-1 mRNA also stimulated activity...
Claudin-1 is an integral membrane protein component of tight junctions. The Snail family transcription factors are repressors that play a central role in the epithelial-mesenchymal transition, process occurs during cancer progression. and Slug members direct E-cadherin act by binding to specific E-boxes its proximal promoter. In present study, we demonstrate overexpression or causes decrease transepithelial electrical resistance. Overexpression MDCK (Madin-Darby canine kidney) cells...
Neuroprotection can be induced by low doses of NMDA, which activate both synaptic and extrasynaptic NMDA receptors. This is in apparent contradiction with our recent findings that receptor signaling exerts a dominant inhibitory effect on prosurvival from Here we report exposure to preconditioning results preferential activation receptors because dramatic increase action potential firing. Both acute long-lasting phases neuroprotection the face apoptotic or excitotoxic insults are dependent...
NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting will impair NMDAR-dependent prosurvival plasticity signaling. We show that promote death independently ligand, when expressed cells...
Synaptic activity promotes resistance to diverse apoptotic insults, the mechanism behind which is incompletely understood. We show here that a coordinated downregulation of core components intrinsic apoptosis pathway by neuronal forms key part underlying mechanism. Activity-dependent protection against insults associated with inhibition cytochrome c release in most but not all neurons, indicative anti-apoptotic signaling both upstream and downstream this step. find enhanced firing suppresses...
Peroxiredoxins are an important family of cysteine-based antioxidant enzymes that exert a neuroprotective effect in several models neurodegeneration. However, under oxidative stress they vulnerable to inactivation through hyperoxidation their active site cysteine residues. We show cortical neurons, the chemopreventive inducer 3H-1,2-dithiole-3-thione (D3T), activates transcription factor Nuclear erythroid 2-related (Nrf2), inhibits formation inactivated, hyperoxidized peroxiredoxins...
Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we show the upregulation G9a and H3K9me2 in brains AD patients. Interestingly, treatment with inhibitor (G9ai) SAMP8 mice reversed high levels rescued cognitive decline. A transcriptional profile analysis after G9ai revealed increased gene expression glia maturation factor β (GMFB) mice. Besides, ChIP-seq inhibition showed enrichment promoters associated neural functions. We observed induction...
Activation of gene expression by FOXO transcription factors can promote neuronal death in response to loss trophic support, or oxidative stress. The predominant FOXOs, FOXO1 and FOXO3, the pro-death genes, such as Fas Ligand, Bim Txnip. Neuroprotective signals initiated neurotrophins, growth synaptic activity trigger nuclear export FOXOs via activation PI3K-Akt pathway. One key aspect regulation is that once has returned baseline, return nucleus resume their target genes. Thus,...
Underexpression of the transcriptional coactivator PGC-1α is causally linked to certain neurodegenerative disorders, including Huntington's Disease (HD). HD pathoprogression also associated with aberrant NMDAR activity, in particular an imbalance between synaptic versus extrasynaptic (NMDAR EX ) activity. Here we show that controls activity neurons and its suppression contributes mutant Huntingtin (mHtt)-induced increases vulnerability excitotoxic insults. We found knock-down endogenous...
Article23 July 2021Open Access Transparent process Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development Sergi Casellas-Díaz Department of Cell Biology, Physiology Immunology, Celltec-UB, University Barcelona, Spain Institute Neurosciences, Search more papers by this author Raquel Larramona-Arcas orcid.org/0000-0001-8427-8007 Guillem Riqué-Pujol Paula Tena-Morraja orcid.org/0000-0002-7617-3392 Claudia Müller-Sánchez orcid.org/0000-0002-3654-2683 Marc...
The ability of Ca(2+) influx through the N-methyl d-aspartate subclass glutamate receptor (NMDA receptor) to both kill neurons and promote survival under different circumstances is well established. Here we discuss signal pathways that mediate this dichotomous signalling, factors influence whether an NMDA receptor-dependent results in a net pro-survival or pro-death effect. magnitude activation, be it intensity duration, course very important determining nature response episode activity,...
ABSTRACT The epicardium plays a crucial role in embryonic heart development and adult repair; however, the molecular events underlying its maturation remain unknown. Wt1, one of main markers epicardium, is essential for epicardial function. Here, we analyse transcriptomic profile epicardial-enriched cells at different stages from control epicardial-specific Wt1 knockout (Wt1KO) mice. Transcriptomic cell morphology analyses Wt1KO mice revealed defect process mutant including sustained...
Peroxiredoxins are neuroprotective antioxidant enzymes that reduce hydroperoxides and protect neurons against oxidative stress. However, they can be inactivated through hyperoxidation of their active site cysteine, an event take place in the brain response to insults such as stroke, also normal aging. Synaptic activity promotes reduction hyperoxidized peroxiredoxins neurons, induces expression sulfiredoxin (Srxn1) sestrin 2 (Sesn2) which have been reported mediate this. We investigated...
NMDA receptors (NMDARs) mediate ischemic brain damage, in part through interactions of the PDZ ligand NR2 subunits with domain proteins PSD-95 and neuronal nitric oxide synthase located within NMDAR signaling complex. We have recently shown that this ligand-dependent pathway promotes death via p38 activation. A peptide mimetic NR2B (TAT-NR2B9c) reduces p38-mediated vitro p38-dependent damage vivo. In absence ligand-p38 pathway, such as TAT-NR2B9c-treated neurons, or NMDAR-expressing...
Mitofusin-2 (Mfn2) expression is dysregulated in vascular proliferative disorders and its overexpression attenuates the proliferation of smooth muscle cells (VSMCs) neointimal lesion development after balloon angioplasty. We sought to gain insight into mechanisms that control Mfn2 VSMCs. cloned characterized 2 kb 5′-flanking region human gene. Its TATA-less promoter contains a CpG island. In keeping with this, 5′-rapid amplification cDNA ends revealed six transcriptional start sites (TSSs),...