RESUMO
Post-operative cognitive dysfunction (POCD) is a common complication after surgery due to the usage of anesthetics, such as Sevoflurane, which severely impacts the life quality of patients. Currently, the pathogenesis of Sevoflurane-induced POCD has not been fully elucidated but is reportedly involved with oxidative stress (OS) injury and aggravated inflammation. Phoenixin-20 (PNX-20) is a PNX peptide consisting of 20 amino acids with promising inhibitory effects on OS and inflammation. Herein, we proposed to explore the potential protective function of PNX-20 on Sevoflurane inhalation-induced POCD in rats. Sprague-Dawley (SD) rats were treated with 100 ng/g PNX-20 for 7 days with or without pre-inhalation with 2.2% Sevoflurane. Markedly increased escape latency and decreased time in the target quadrant in the Morris water maze (MWM) test, and aggravated pathological changes and apoptosis in the hippocampus tissue were observed in Sevoflurane-treated rats, which were markedly attenuated by PNX-20. Furthermore, the aggravated inflammation and OS in the hippocampus observed in Sevoflurane-treated rats were notably abolished by PNX-20. Moreover, the brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), and phospho-cAMP response element binding protein/cAMP response element binding protein (p-CREB/CREB) levels were markedly decreased in Sevoflurane-treated rats, which were memorably increased by PNX-20. Our results indicated that PNX-20 ameliorated Sevoflurane inhalation-induced POCD in rats via the activation of PKA/CREB signaling, which might supply a new treatment approach for POCD.
Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Animais , Humanos , Ratos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Complicações Cognitivas Pós-Operatórias/metabolismo , Ratos Sprague-Dawley , Sevoflurano/efeitos adversos , Sevoflurano/farmacologia , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/efeitos dos fármacos , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/metabolismoRESUMO
BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats' liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes.
Assuntos
Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/efeitos dos fármacos , Glicolipídeos/metabolismo , Éteres Difenil Halogenados/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colesterol/sangue , Humanos , Fígado/metabolismo , Masculino , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , TriglicerídeosAssuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Proteínas de Choque Térmico HSP40/genética , Neoplasias Hepáticas/genética , Proteínas de Fusão Oncogênica/genética , Carcinoma Hepatocelular/tratamento farmacológico , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/efeitos dos fármacos , Proteínas de Choque Térmico HSP40/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas de Fusão Oncogênica/efeitos dos fármacosRESUMO
Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. Thus, it is extremely important to prevent memory decline for increasing healthy aging. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect, but the preventive role on memory impairment and the underlying mechanisms have not been well determined. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside 100mg/kg per day for 8 months. Placebo-treated aged mice, young and adult ones (4- and 8-month-old, respectively) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Compared with aged control group, the plasticity-related proteins including phospho-N-methyl-d-aspartate receptor1 (NMDAR1), phospho-calcium-calmodulin dependent kinase II (CaMK II), phospho-PKA catalytic beta subunit (PKA Cbeta), phospho-cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) in hippocampus significantly increased in ginsenoside treated group. These findings suggest that ginsenoside is effective on the prevention of age-related memory impairment, and the up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms.
