10 results on '"Francesca Copperi"'
Search Results
2. Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions
- Author
-
Francesca Copperi, Jung Dae Kim, and Sabrina Diano
- Subjects
melanocortin system ,cardiovascular functions ,α-MSH ,γ-MSH ,MC3R ,MC4R ,Physiology ,QP1-981 - Abstract
Increasing evidence indicates that the melanocortin system is not only a central player in energy homeostasis, food intake and glucose level regulation, but also in the modulation of cardiovascular functions, such as blood pressure and heart rate. The melanocortins, and in particular α- and γ-MSH, have been shown to exert their cardiovascular activity both at the central nervous system level and in the periphery (e.g., in the adrenal gland), binding their receptors MC3R and MC4R and influencing the activity of the sympathetic nervous system. In addition, some studies have shown that the activation of MC3R and MC4R by their endogenous ligands is able to improve the outcome of cardiovascular diseases, such as myocardial and cerebral ischemia. In this brief review, we will discuss the current knowledge of how the melanocortin system influences essential cardiovascular functions, such as blood pressure and heart rate, and its protective role in ischemic events, with a particular focus on the central regulation of such mechanisms.
- Published
- 2021
- Full Text
- View/download PDF
3. Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis
- Author
-
Carlo C. Campa, Rangel L. Silva, Jean P. Margaria, Tracey Pirali, Matheus S. Mattos, Lucas R. Kraemer, Diego C. Reis, Giorgio Grosa, Francesca Copperi, Eduardo M. Dalmarco, Roberto C. P. Lima-Júnior, Silvio Aprile, Valentina Sala, Federica Dal Bello, Douglas Silva Prado, Jose Carlos Alves-Filho, Claudio Medana, Geovanni D. Cassali, Gian Cesare Tron, Mauro M. Teixeira, Elisa Ciraolo, Remo C. Russo, and Emilio Hirsch
- Subjects
Science - Abstract
Activation of PI3K plays a role in pulmonary inflammation. Here, the authors develop a drug inhibitor of PI3K, and show that it inhibits lung inflammation and damage in mouse models of asthma and lung fibrosis.
- Published
- 2018
- Full Text
- View/download PDF
4. EBI2 is a negative modulator of brown adipose tissue energy expenditure in mice and human brown adipocytes
- Author
-
Francesca, Copperi, Inna, Schleis, Martin, Roumain, Giulio G, Muccioli, Stefano, Casola, Martin, Klingenspor, Alexander, Pfeifer, Thorsten, Gnad, and UCL - SSS/LDRI - Louvain Drug Research Institute
- Subjects
Mice ,Norepinephrine ,Adipocytes, Brown ,Adipose Tissue, Brown ,Animals ,Humans ,Thermogenesis ,Energy Metabolism ,Receptors, G-Protein-Coupled - Abstract
Pharmacological activation of brown adipose tissue (BAT) is an attractive approach for increasing energy expenditure to counteract obesity. Given the side-effects of known activators of BAT, we studied inhibitors of BAT as a novel, alternative concept to regulate energy expenditure. We focused on G-protein-coupled receptors that are one of the major targets of clinically used drugs. Here, we identify GPR183, also known as EBI2, as the most highly expressed inhibitory G-protein-coupled receptor in BAT among the receptors examined. Activation of EBI2 using its endogenous ligand 7α,25-dihydroxycholesterol significantly decreases BAT-mediated energy expenditure in mice. In contrast, mice deficient for EBI2 show increased energy dissipation in response to cold. Interestingly, only thermogenic adipose tissue depots - BAT and subcutaneous white adipose tissue -respond to 7α,25-dihydroxycholesterol treatment/EBI2 activation but not gonadal white fat, which has the lowest thermogenic capacity. EBI2 activation in brown adipocytes significantly reduces norepinephrine-induced cAMP production, whereas pharmacological inhibition or genetic ablation of EBI2 results in an increased response. Importantly, EBI2 significantly inhibits norepinephrine-induced activation of human brown adipocytes. Our data identify the 7α,25-dihydroxycholesterol/EBI2 signaling pathway as a so far unknown BAT inhibitor. Understanding the inhibitory regulation of BAT might lead to novel pharmacological approaches to increase the activity of thermogenic adipose tissue and whole body energy expenditure in humans.
- Published
- 2022
5. MELANOCORTIN SIGNALING CONNECTING SYSTEMIC METABOLISM WITH MOOD DISORDERS
- Author
-
Sabrina Diano, Francesca Copperi, and Jung Dae Kim
- Subjects
0301 basic medicine ,media_common.quotation_subject ,Melancholic depression ,Article ,03 medical and health sciences ,0302 clinical medicine ,Central melanocortin system ,medicine ,Animals ,Neuropeptide Y ,Obesity ,Atypical depression ,Biological Psychiatry ,media_common ,Depressive Disorder, Major ,business.industry ,Mood Disorders ,Anhedonia ,Appetite ,medicine.disease ,Melanocortins ,030104 developmental biology ,medicine.anatomical_structure ,Mood ,Mood disorders ,medicine.symptom ,Melanocortin ,business ,Energy Metabolism ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Obesity and mood disorders are often overlapping pathologies that are prevalent public health concerns. Many studies have indicated a positive correlation between depression and obesity, although weight loss and decreased appetite are also recognized as features of depression. Accordingly, the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) defines two subtypes of depression associated with changes in feeding: melancholic depression, characterized by anhedonia and associated with decreased feeding and appetite, and atypical depression, characterized by fatigue, sleepiness, hyperphagia and weight gain. The central nervous system plays a key role in the regulation of feeding and mood, thus suggesting that overlapping neuronal circuits may be involved in their modulation. However, these circuits have yet to be completely characterized. The central melanocortin system, a circuitry characterized by the expression of specific peptides (proopiomelanocortins, agouti gene-related protein and neuropeptide Y) and their receptors (MCRs), has been shown to be a key player in the regulation of feeding. In addition, the melanocortin system has also been shown to affect anxiety and depressive-like behavior, thus suggesting a possible role of the melanocortin system as a biological substrate linking feeding and depression. However, more studies are needed to fully understand this complex system and its role in regulating metabolic and mood disorders. In this review, we will discuss the current literature on the role of the melanocortin system in human and animal models in feeding and mood regulation, providing evidence of the biological interplay between anxiety, major depressive disorders, appetite and body weight regulation.
- Published
- 2021
6. Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
- Author
-
Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhäuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian Brinkmann, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K. Eltzschig, Tarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K. Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A. Virtanen, and Alexander Pfeifer
- Subjects
Physiology ,Cell Biology ,Molecular Biology - Published
- 2022
7. Rab11 activity and PtdIns(3)P turnover removes recycling cargo from endosomes
- Author
-
Maria Chiara De Santis, Carlo Cosimo Campa, Emilio Hirsch, Carla Bosia, Abhishek Derle, Marco Del Giudice, Jean Piero Margaria, Luca Gozzelino, and Francesca Copperi
- Subjects
0301 basic medicine ,Endosome ,Dynein ,PROTEIN ,Endocytic recycling ,Endosomes ,RESONANCE ENERGY-TRANSFER ,ACTIVATION ,DYNEIN ,03 medical and health sciences ,chemistry.chemical_compound ,TRAFFICKING ,PI(3)P ,CELLS ,COMPARTMENT ,STABILITY ,TRANSPORT ,Chlorocebus aethiops ,Animals ,Humans ,Small GTPase ,Phosphatidylinositol ,Molecular Biology ,Cell Biology ,Compartment (chemistry) ,Phosphoric Monoester Hydrolases ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Förster resonance energy transfer ,chemistry ,rab GTP-Binding Proteins ,COS Cells ,Myotubularin 1 - Abstract
Directional transport of recycling cargo from early endosomes (EE) to the endocytic recycling compartment (ERC) relies on phosphatidylinositol 3-phosphate (PtdIns(3)P) hydrolysis and activation of the small GTPase Rab11. However, how these events are coordinated is yet unclear. By using a novel genetically-encoded FRET biosensor for Rab11, we report that generation of endosomal PtdIns(3)P by the clathrin-binding phosphoinositide 3-kinase class 2 alpha (PI3K-C2α) controls the activation of Rab11. Active Rab11, in turn, prompts the recruitment of the phosphatidylinositol 3-phosphatase myotubularin 1 (MTM1), eventually enabling the release of recycling cargo from the EE and its delivery toward the ERC. Our findings thus define that delivery of recycling cargo toward the ERC requires spatial and sequential coupling of Rab11 activity with PtdIns(3)P turnover.
- Published
- 2018
8. Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
- Author
-
Aileen Hochhäuser, Camilla Scheele, Christian Dani, Thorsten Gnad, Frank Suhr, Saskia Haufs-Brusberg, Volodymyr Tsvilovskyy, Peter Brust, Arnau Cordomí, Minna Lahesmaa, Wilhelm Bloch, Markku Taittonen, Matthias Blüher, Mathias Kranz, Leonardo Pardo, Daniela Wenzel, Holger K. Eltzschig, Laia Reverte-Salisa, Francesca Copperi, Alexander Pfeifer, Gemma Navarro, Rafael Franco, Tarja Niemi, Jennifer Naumann, Pirjo Nuutila, Winnie Deuther-Conrad, Christian Brinkmann, Bernd K. Fleischmann, Naja Z. Jespersen, Joern Rittweger, and Kirsi A. Virtanen
- Subjects
Male ,0301 basic medicine ,Aging ,muscle ,Physiology ,Adipose tissue ,BEIGE ADIPOCYTES ,White adipose tissue ,Population aging ,Mice ,GPCR ,Regulació del metabolisme ,0302 clinical medicine ,FUNCTIONAL-CHARACTERIZATION ,energy metabolism ,Brown adipose tissue ,Myocyte ,Cells, Cultured ,DOPAMINE D-1 ,Mice, Knockout ,BROWN ADIPOSE-TISSUE ,Middle Aged ,Muscle atrophy ,medicine.anatomical_structure ,adenosine ,SKELETAL-MUSCLE ,Obesitat ,medicine.symptom ,Life Sciences & Biomedicine ,STEM-CELLS ,Signal Transduction ,Adult ,medicine.medical_specialty ,Adolescent ,CROSS-TALK ,Mice, Transgenic ,Biology ,Receptor, Adenosine A2B ,Article ,sarcopenia ,Endocrinology & Metabolism ,Young Adult ,03 medical and health sciences ,Envelliment de la població ,Metabolic regulation ,Internal medicine ,adenosine receptor A2B ,medicine ,Animals ,Humans ,SARCOPENIC OBESITY ,INTERNATIONAL UNION ,Obesity ,Molecular Biology ,browning ,Science & Technology ,Skeletal muscle ,brown adipose tissue ,Cell Biology ,Adenosine Receptor A2b ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,FAT ,030217 neurology & neurosurgery ,Adenosine A2B receptor - Abstract
The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential. ispartof: Cell Metabolism vol:32 issue:1 pages:56+-56+ ispartof: location:United States status: Published online
- Published
- 2020
9. Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis
- Author
-
Valentina Sala, Diego Carlos dos Reis, Eduardo Monguilhott Dalmarco, Mauro M. Teixeira, Emilio Hirsch, Gian Cesare Tron, Federica Dal Bello, Giorgio Grosa, Jean Piero Margaria, Geovanni Dantas Cassali, Roberto C. P. Lima-Júnior, Lucas Kraemer, Francesca Copperi, Remo Castro Russo, Carlo Cosimo Campa, Claudio Medana, Douglas Silva Prado, José C. Alves-Filho, Matheus Silvério Mattos, Elisa Ciraolo, Silvio Aprile, Tracey Pirali, and Rangel L. Silva
- Subjects
0301 basic medicine ,Genetics and Molecular Biology (all) ,Pulmonary Fibrosis ,PATHOGENESIS ,General Physics and Astronomy ,Pharmacology ,Inbred C57BL ,Biochemistry ,THERAPIES ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,Mice ,0302 clinical medicine ,Fibrosis ,Pulmonary fibrosis ,Benzene Derivatives ,Enzyme Inhibitors ,Phosphorylation ,lcsh:Science ,Inbred BALB C ,Phosphoinositide-3 Kinase Inhibitors ,Mice, Inbred BALB C ,Multidisciplinary ,Inhalation ,PHOSPHOINOSITIDE 3-KINASE GAMMA ,Chemistry (all) ,Esters ,Prodrug ,respiratory system ,Multidisciplinary Sciences ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Administration ,Science & Technology - Other Topics ,medicine.symptom ,Ovalbumin ,Science ,Inflammation ,Bleomycin ,General Biochemistry, Genetics and Molecular Biology ,Article ,MECHANISMS ,03 medical and health sciences ,Physics and Astronomy (all) ,INFLAMMATION ,Administration, Inhalation ,medicine ,Animals ,Asthma ,Disease Models, Animal ,Mice, Inbred C57BL ,Proto-Oncogene Proteins c-akt ,Biochemistry, Genetics and Molecular Biology (all) ,ANIMAIS DE LABORATÓRIO ,P110-DELTA ,Lung ,Science & Technology ,RECEPTOR ,business.industry ,Animal ,General Chemistry ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,chemistry ,Cardiovascular and Metabolic Diseases ,Disease Models ,T-CELLS ,lcsh:Q ,business ,CLASS-IA PI3K ,RESPONSES - Abstract
PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis., Activation of PI3K plays a role in pulmonary inflammation. Here, the authors develop a drug inhibitor of PI3K, and show that it inhibits lung inflammation and damage in mouse models of asthma and lung fibrosis.
- Published
- 2018
10. Rac signal adaptation controls neutrophil mobilization from the bone marrow
- Author
-
Giulia Germena, Christoph Scheiermann, Irene Franco, Andrea Antonio Gamba, Augusta Di Savino, Alessandra Ghigo, Remco T. A. Megens, Emilio Hirsch, Francesca Copperi, Markus Sperandio, Angela R.M. Kurz, Miriam Martini, Anna Sapienza, Alessia Perino, Elisa Ciraolo, Carlo Cosimo Campa, Annalisa Camporeale, Biomedische Technologie, RS: CARIM School for Cardiovascular Diseases, RS: CARIM - R3.07 - Structure-function analysis of the chemokine interactome for therapeutic targeting and imaging in atherosclerosis, and RS: CARIM - R1.01 - Blood proteins & engineering
- Subjects
0301 basic medicine ,Chemokine ,Receptors, CXCR4 ,Neutrophils ,Knockout ,CXCR4 ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Bone Marrow ,Receptors ,medicine ,Animals ,CXC chemokine receptors ,Receptor ,Molecular Biology ,Mice, Knockout ,biology ,Signal Transduction/physiology ,GTPase-Activating Proteins ,Cell migration ,Chemotaxis ,Cell Biology ,CXCR4/genetics/metabolism ,Chemokine CXCL12 ,Cell biology ,rac GTP-Binding Proteins ,CXCL2 ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,GTPase-Activating Proteins/genetics/metabolism ,Immunology ,Bone Marrow/enzymology ,biology.protein ,Neutrophils/enzymology ,Bone marrow ,Rac GTP-Binding Proteins/genetics/metabolism ,Chemokine CXCL12/genetics/metabolism ,Signal Transduction - Abstract
Mobilization of neutrophils from the bone marrow determines neutrophil blood counts and thus is medically important. Balanced neutrophil mobilization from the bone marrow depends on the retention-promoting chemokine CXCL12 and its receptor CXCR4 and the egression-promoting chemokine CXCL2 and its receptor CXCR2. Both pathways activate the small guanosine triphosphatase Rac, leaving the role of this signaling event in neutrophil retention and egression ambiguous. On the assumption that active Rac determines persistent directional cell migration, we generated a mathematical model to link chemokine-mediated Rac modulation to neutrophil egression time. Our computer simulation indicated that, in the bone marrow, where the retention signal predominated, egression time strictly depended on the time it took Rac to return to its basal activity (namely, adaptation). This prediction was validated in mice lacking the Rac inhibitor ArhGAP15. Neutrophils in these mice showed prolonged Rac adaptation and cell-autonomous retention in the bone marrow. Our model thus demonstrates that mobilization in the presence of two spatially defined opposing chemotactic cues strictly depends on inhibitors shaping the time course of signal adaptation. Furthermore, our findings might help to find new modes of intervention to treat conditions characterized by excessively low or high circulating neutrophils.
- Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.