Proteomic quantitative study of dorsal root ganglia and sciatic nerve in type 2 diabetic mice
Autor: | Assumpció Bosch, Xavier Navarro, Sergi Verdés, Andrea Onieva, Marc Leal-Julià, Miguel Chillón, Ángela María Muñoz Sánchez, Jorge J. Vilches |
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Přispěvatelé: | Institut Català de la Salut, [Leal-Julià M, Onieva A, Verdés S, Sánchez Á] Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta UAB-VHIR, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Vilches JJ] Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Chillón M] Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institut Català de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Unitat Mixta UAB-VHIR, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Navarro X] Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain. [Bosch A] Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain. Unitat Mixta UAB-VHIR, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
Proteomics enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES] Diabetic neuropathy Pharmacology Diabetis no-insulinodependent Mice Diabetic Neuropathies Ganglia Spinal Nervous System::Ganglia::Ganglia Sensory::Ganglia Spinal [ANATOMY] Medicine Ratolins sistema nervioso::sistema nervioso periférico::nervios periféricos::nervios espinales::plexo lumbosacro::nervio ciático [ANATOMÍA] Dorsal root ganglia Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS] Internal medicine Diabetes Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus Type 2 [DISEASES] Sistema nerviós simpàtic Hyperalgesia Receptors Leptin Female Original Article Sciatic nerve medicine.symptom Nervous System::Peripheral Nervous System::Peripheral Nerves::Spinal Nerves::Lumbosacral Plexus::Sciatic Nerve [ANATOMY] Proteòmica Ciàtica Diabetes Mellitus Experimental Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics [DISCIPLINES AND OCCUPATIONS] Downregulation and upregulation Diabetes mellitus Animals sistema nervioso::ganglios::ganglios sensoriales::ganglios espinales [ANATOMÍA] Obesity Molecular Biology Leptin receptor business.industry disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::bioquímica::proteómica [DISCIPLINAS Y OCUPACIONES] Dysautonomia Cell Biology medicine.disease RC31-1245 Neuropathy Disease Models Animal Peripheral neuropathy Diabetes Mellitus Type 2 business Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS] |
Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 55, Iss, Pp 101408-(2022) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientia |
Popis: | Objective Peripheral neuropathy is the most common and debilitating complication of type 2 diabetes, leading to sensory loss, dysautonomia, hyperalgesia, and spontaneous noxious sensations. Despite the clinical and economic burden of diabetic neuropathy, no effective treatment is available. More preclinical research must be conducted in order to gain further understanding of the aetiology of the disease and elucidate new therapeutic targets. Methods The proteome of lumbar dorsal root ganglia and sciatic nerve of BKS-db/db mice, which contain a mutation of the leptin receptor and are an established type 2 diabetes model, was characterized for the first time by tandem mass tag labelling and mass spectrometry analysis. Results Proteomic analysis showed differentially expressed proteins grouped into functional clusters in db/db peripheral nerves compared to control mice, underlining reduced glycolytic and TCA cycle metabolism, higher lipid catabolism, upregulation of muscle-like proteins in DRG and downregulation in SCN, increased cytoskeleton-related proteins, a mild dysregulation of folding chaperones, activation of acute-phase and inflammatory response, and alterations in glutathione metabolism and oxidative stress related proteins. Conclusions Our data validate previous transcriptomic and metabolomic results and uncover new pathways altered in diabetic neuropathy. Our results point out that energetic deficiency could represent the main mechanism of neurodegeneration observed in diabetic neuropathy. These findings may provide important information to select appropriate targets to develop new therapeutic strategies. Highlights • Unprecedent proteomic analysis of DRG and sciatic nerve from db/db mouse. • Oxidative stress, inflammation and cytoskeleton abnormalities are linked to neuropathy. • Low ATP and energetic imbalance mediate neurodegeneration in diabetic neuropathy. |
Databáze: | OpenAIRE |
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