Proteomic quantitative study of dorsal root ganglia and sciatic nerve in type 2 diabetic mice
Leal Julia, Marc (Hospital Universitari Vall d'Hebron)
Vilches Herráez, Jorge Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Onieva Salgado, Andrea (Vall d'Hebron Institut de Recerca (VHIR))
Verdés, Sergi (Vall d'Hebron Institut de Recerca (VHIR))
Sánchez, Ángela (Vall d'Hebron Institut de Recerca (VHIR))
Chillón Rodríguez, Miguel (Vall d'Hebron Institut de Recerca (VHIR))
Navarro, X. (Xavier) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Bosch i Merino, Assumpció (Vall d'Hebron Institut de Recerca (VHIR))

Data:	2021
Resum:	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. 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. 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. 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Diabetes ; Obesity ; Neuropathy ; Proteomics ; Dorsal root ganglia ; Sciatic nerve
Publicat a:	Molecular metabolism, Vol. 55 (november 2021) , ISSN 2212-8778

DOI: 10.1016/j.molmet.2021.101408
PMID: 34856394

13 p, 3.1 MB

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