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Aging (Albany NY) ; 13(14): 19013-19027, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326274

RESUMO

BACKGROUNDS AND AIMS: The role of peroxisome proliferator activated receptor-γ (PPAR-γ) in neuronal apoptosis remains unclear. We aim to investigate the role of PPAR-γ in glucagon-like peptide-1 (GLP-1) alleviated neuronal apoptosis induced by carboxymethyl-lysine (CML). MATERIALS AND METHODS: In vitro, PC12 cells were treated by CML/GLP-1. Moreover. the function of PPAR-γ was blocked by GW9662. In vivo, streptozotocin (STZ) was used to induce diabetic rats with neuronal apoptosis. The cognitive function of rats was observed by Morris water maze. Apoptosis was detected by TUNEL assay. Bcl2, Bax, PPAR-γ and receptor of GLP-1 (GLP-1R) were measured by western blotting or immunofluorescence. RESULTS: In vitro experiment, CML triggered apoptosis, down-regulated GLP-1R and PPAR-γ. Moreover, GLP-1 not only alleviated the apoptosis, but also increased levels of PPAR-γ. GW9662 abolished the neuroprotective effect of GLP-1 on PC12 cells from apoptosis. Furthermore, GLP-1R promoter sequences were detected in the PPAR-γ antibody pulled mixture. GPL-1 levels decreased, while CML levels increased in diabetic rats, compared with control rats. Additionally, we observed elevated bax, decreased bcl2, GLP-1R and PPAR-γ in diabetic rats. CONCLUSIONS: GLP-1 could attenuate neuronal apoptosis induced by CML. Additionally, PPAR-γ involves in this process.


Assuntos
Doença de Alzheimer , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Lisina/análogos & derivados , Fármacos Neuroprotetores , PPAR gama/metabolismo , Doença de Alzheimer/metabolismo , Animais , Apoptose , Encéfalo/efeitos dos fármacos , Cognição , Diabetes Mellitus Experimental/complicações , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Lisina/efeitos adversos , Lisina/metabolismo , Masculino , Aprendizagem em Labirinto , Neurônios , Células PC12 , Peroxissomos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/metabolismo
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