RESUMO
Accumulating evidence suggests that resveratrol may have beneficial effects against traumatic brain injury. However, its effect on the regulation of extracellular levels of gliotransmitter and on the activation of p38 MAPK in astrocytes is still unknown. We have examined whether resveratrol regulates extracellular levels of gliotransmitter as well as the activation of p38 MAPK in cultured astrocytes before and after stretch injury. The extracellular levels of glutamate, D-/L-serine and D-serine were apparently reduced by 100 µM resveratrol in control astrocyte cultures. The dramatic increase of glutamate and D-serine release induced by stretch injury was also clearly inhibited by resveratrol. Resveratrol mediates this response by reduction of release through inhibition of extracellular calcium influx and increment of gliotransmitter uptake through enhancement of amino acid transporter expressed in the membrane of astrocyte. In addition, resveratrol definitely reduced the activation of p38 MAPK in cultured astrocytes following stretch injury. AMPA receptor is involved in the activation of p38 following injury. Conversely, the levels of glutamine and glycine were not obviously affected by resveratrol before and after injury. Intracellular levels of glutamate and D-serine are not apparently changed by stretch injury. Collectively, our data suggest that resveratrol might play an important role in protection of the nervous system after injury by decreasing the extracellular levels of gliotransmitter and inhibiting activation of p38 MAPK following injury.
Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Inibidores Enzimáticos/farmacologia , Neurotransmissores/metabolismo , Estilbenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Aminoácidos/metabolismo , Animais , Astrócitos/citologia , Cálcio/metabolismo , Células Cultivadas , Quelantes/farmacologia , Meios de Cultura/química , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Transportador 2 de Aminoácido Excitatório/metabolismo , Camundongos , Resveratrol , Serina/metabolismo , Estresse MecânicoRESUMO
OBJECTIVE: A meta-analysis was applied to evaluate the associations between tumor necrosis factor-α (TNF-α) -308G>A (rs1800629) polymorphism and type 2 diabetes mellitus (T2DM). METHODS: Hardy-Weinberg equilibrium (HWE) was employed to test genetic equilibrium among the genotypes of the selected literature. Power analysis was performed with the Power and Sample Size Calculation (PS) program. A fixed or random effect model was used on the basis of heterogeneity. Publication bias was quantified and examined with the Begg's funnel plot test and Egger's linear regression test. The meta-analysis was performed with Review Manager 5.1 and Stata 11.0. RESULTS: There were 10 studies including 1425 T2DM patients and 1116 healthy control subjects involved in this meta-analysis. No significant publication bias was found in the studies. The pooled ORs (95% CIs) for TNF-α -308G>A of A vs. G allele and GA+AA vs. GG genotype were 1.63 (1.17-2.25) and 1.47 (1.17-1.85), respectively. CONCLUSION: This meta-analysis result suggested that TNF-α -308G>A polymorphism was strongly associated with T2DM risk, and A allele at this locus might be a susceptibility allele for the development of T2DM in Han Chinese population.
Assuntos
Povo Asiático/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/genética , Estudos de Associação Genética , Genótipo , Humanos , Modelos Lineares , Modelos Genéticos , Razão de Chances , Viés de PublicaçãoRESUMO
OBJECTIVE: To study the effects of resveratrol on amino acid release in cultured astrocytes with stretch injury and explore its possible mechanism for central nervous system protection. METHODS: Cultured rat astrocytes were treated with different concentrations of resveratrol for 12 h and the subsequent changes in Glu and Gln release and lactate dehydrogenase(LDH) leakage were examined after stretch injury. RESULTS: High-performance liquid chromatography showed that stretch injury increased Glu release from the astrocytes (P<0.05), and at the concentration of 1 micromol/L, resveratrol further increased Glu release (P<0.05), whereas at 100 micromol/L, resveratrol obviously inhibit Glu release (P<0.05). LDH leakage increased significantly after stretch injury of the astrocytes (P<0.05), and resveratrol acted to further increase LDH leakage at 1 micromol/L but inhibited LDH leakage at 100 micromol/L (P<0.05). CONCLUSION: Resveratrol can inhibit the release of Glu and LDH leakage from rat astrocytes to protect the cells from stretch injury.