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Melatonin ameliorates cerebral ischemia-reperfusion injury in diabetic mice by enhancing autophagy via the SIRT1-BMAL1 pathway.
Liu, Lian; Cao, Quan; Gao, Wenwei; Li, Bing-Yu; Zeng, Cheng; Xia, Zhongyuan; Zhao, Bo.
Afiliação
  • Liu L; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Cao Q; Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China.
  • Gao W; Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
  • Li BY; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Zeng C; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Xia Z; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Zhao B; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
FASEB J ; 35(12): e22040, 2021 12.
Article em En | MEDLINE | ID: mdl-34800293
ABSTRACT
Diabetic brains are more vulnerable to ischemia-reperfusion injury. Previous studies have proved that melatonin could protect against cerebral ischemia-reperfusion (CIR) injury in non-diabetic stroke models; however, its roles and the underlying mechanisms against CIR injury in diabetic mice remain unknown. Streptozotocin-induced diabetic mice and high-glucose-cultured HT22 cells were exposed to melatonin, with or without administration of the autophagy inhibitor 3-methyladenine (3-MA) and the specifically silent information regulator 1 (SIRT1) inhibitor EX527, and then subjected to CIR or oxygen-glucose deprivation/reperfusion operation. We found that diabetic mice showed aggravated brain damage, increased apoptosis and oxidative stress, and deficient autophagy following CIR compared with non-diabetic counterparts. Melatonin treatment exhibited improved histological damage, neurological outcomes, and cerebral infarct size. Intriguingly, melatonin markedly increased cell survival, anti-oxidative and anti-apoptosis effects, and significantly enhanced autophagy. However, these effects were largely attenuated by 3-MA or EX527. Additionally, our cellular experiments demonstrated that melatonin increased the SIRT1-BMAL1 pathway-related proteins' expression in a dose-dependent manner. In conclusion, these results indicate that melatonin treatment can protect against CIR-induced brain damage in diabetic mice, which may be achieved by the autophagy enhancement mediated by the SIRT1-BMAL1 pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Traumatismo por Reperfusão / Isquemia Encefálica / Diabetes Mellitus Experimental / Sirtuína 1 / Fatores de Transcrição ARNTL / Melatonina Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Traumatismo por Reperfusão / Isquemia Encefálica / Diabetes Mellitus Experimental / Sirtuína 1 / Fatores de Transcrição ARNTL / Melatonina Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China