Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Adv Exp Med Biol ; 1155: 463-470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468423

RESUMO

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4 mg/L As2O3 via drinking water for 60 days. Group 3, taurine protection group, was treated with 4 mg/L As2O3 and 150 mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.


Assuntos
Arsênio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estresse Oxidativo , Taurina/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Suplementos Nutricionais , Glutationa/análise , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Malondialdeído/análise , Camundongos , Distribuição Aleatória
2.
Adv Exp Med Biol ; 1155: 739-746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468444

RESUMO

The herbicide Paraquat induce oxidative stress-mediated lung injury. Taurine is a well-known antioxidant. This study was designed to explore the effect of taurine on paraquat-induced injury and its related mechanism in A549 cells. The cells were pretreated with various concentrations of taurine for 30 min prior to paraquat exposure. 24 h later, cell viability was examined by the MTT assay. The level of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were analyzed. The results show that taurine treatment significantly attenuates the decrease in cell viability mediated by paraquat in A549 cells. Taurine also reversed paraquat-induced disturbances in GSH content and GPx activity. Taurine exerts protection against paraquat-mediated A549 cell toxicity likely through modulation of oxidative stress.


Assuntos
Células Epiteliais/efeitos dos fármacos , Estresse Oxidativo , Paraquat/toxicidade , Taurina/farmacologia , Células A549 , Células Cultivadas , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Pulmão/citologia
3.
DNA Repair (Amst) ; 74: 51-62, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30630676

RESUMO

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. We showed that the Spy1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro by qRT-PCR, western blotting, and Immunoassay tests. In addition, we established that over-expression of human SOD1 mutant G93A led to a decreased expression of Spy1. Furthermore, DNA damage response was activated in SOD1G93A-transfected cells (mSOD1 cells). Moreover, decreased Spy1 expression reduced cell viability and further activated the DNA damage response in mSOD1 cells. In contrast, increased Spy1 expression improved cell viability and inhibited the DNA damage response in mSOD1 cells. These results suggest that Spy1 plays a protective role in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS as well as for trial designs, such as investigating the role of oncogenic proteins in ALS.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA/genética , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Mutação , Superóxido Dismutase-1/genética , Animais , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/genética , Linhagem Celular , Sobrevivência Celular , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos
4.
Mol Cell Neurosci ; 68: 303-13, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26320681

RESUMO

Astrocyte elevated gene-1 (AEG-1) has been reported to regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and is also regulated by it. This study investigated how AEG-1 participates in the survival pathway of motor neurons in amyotrophic lateral sclerosis (ALS). We found reduced levels of AEG-1 in ALS motor neurons, both in vivo and in vitro, compared to wild type controls. Moreover, AEG-1 silencing demonstrated inhibition of the PI3K/Akt pathway and increased cell apoptosis. Additionally, the PI3K/Akt pathway in mSOD1 cells was unresponsive under serum deprivation conditions compared to wtSOD1 cells. These results suggest that AEG-1 deficiency, together with the inhibited PI3K/Akt pathway was associated with decreased viability of ALS motor neurons. However, the mRNA levels of AEG-1 were still lower in mSOD1 cells compared to the control groups, though the signaling pathway was activated by application of a PI3-K activator. This suggests that in ALS motor neurons, some unknown interruption exists in the PI3K/Akt/CREB/AEG-1 feedback loop, thus attenuating the protection by this signaling pathway. Together, these findings support that AEG-1 is a critical factor for cell survival, and the disrupted PI3K/Akt/CREB/AEG-1cycle is involved in the death of injured motor neurons and pathogenesis of ALS.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Proteínas de Membrana/metabolismo , Neurônios Motores/patologia , Transdução de Sinais/fisiologia , Esclerose Lateral Amiotrófica/genética , Animais , Apoptose/genética , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Embrião de Mamíferos , Feminino , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios Motores/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA/fisiologia , RNA Interferente Pequeno/farmacologia , Proteínas de Ligação a RNA , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/patologia , Superóxido Dismutase/genética
5.
Neurotoxicology ; 48: 171-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25845300

RESUMO

Approximately half of those who survive severe carbon monoxide (CO) poisoning develop delayed neurologic sequelae. Growing evidence supports the crucial role of free radicals in delayed brain injury associated with CO toxicity. Xanthine oxidase (XO) has been reported to play a pivotal role in the generation of reactive oxygen species (ROS) in CO poisoning. A recent report indicates that allopurinol both attenuated oxidative stress and possessed anti-inflammatory properties in an animal model of acute liver failure. In this study, we aimed to explore the potential of allopurinol to reduce the severity of delayed neurologic sequelae. The rats were first exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO poisoning, the rats were injected with allopurinol (50 mg/kg, i.p.) six times. Results showed that allopurinol significantly reduced neuronal death and suppressed expression of pro-inflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, ionized calcium-binding adapter molecule 1, and degraded myelin basic protein. Furthermore, behavioral studies revealed an improved performance in the Morris water maze test. Our findings indicated that allopurinol may have protective effects against delayed neurologic sequelae caused by CO toxicity.


Assuntos
Alopurinol/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/fisiopatologia , Intoxicação por Monóxido de Carbono/psicologia , Morte Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA