RESUMEN
Pinelliae Rhizoma has been used traditionally as an antidepressant in Oriental medicine. In this study, the effect of Pinelliae Rhizoma extract (PRe) on psychological stress was investigated in mice. The results of an elevated plus-maze experiment revealed that application of psychological stress to mice led to the development of an abnormal behavioral pattern. However, oral administration of PRe significantly reduced the abnormal behavior of mice with a recovery rate of 75.5%. To elucidate the molecular mechanism by PRe, a microarray analysis of the brains of mice was conducted. The results of this analysis revealed that 456 genes were up-regulated and 392 genes were down-regulated in response to psychological stress. The expression of most of the genes that were altered in response to psychological stress was restored to normal levels in PRe treated mice, with a recovery rate of 81.5% and 85.2% being observed for up- and down-regulated genes, respectively. Finally, when the interaction network information was analysed, the recovery rate of the core node genes (46 up- and 29 down-regulated genes) in PRe treated mice was found to be over 95%, which indicates that this final set of genes may be the effective target of PRe.
Asunto(s)
Perfilación de la Expresión Génica , Pinellia/química , Extractos Vegetales/uso terapéutico , Estrés Psicológico/tratamiento farmacológico , Animales , Encéfalo/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Análisis de Secuencia por Matrices de Oligonucleótidos , FitoterapiaRESUMEN
The effect of poly(ADP-ribosyl)ation on the stability of p53 in SK-HEP1 cells treated with UV light was examined. Intracellular levels of p53 increased in cells treated with a low dose of UV light (20 J/m2), whereas they increased but then declined after a higher dose of UV (100 J/m2). Intracellular levels of p53 in the UV treated SK-HEP1 cells were dependent on the UV dose. Use of proteasome inhibitors revealed that p53 is degraded by proteasomal proteolysis after high doses of UV light. We present evidence that, at low doses, poly(ADP-ribose)polymerase (PARP) poly(ADP-ribosyl)ates p53 and protects it from proteasomal degradation before caspase-3 is activated, whereas at high doses the cells undergo UV induced apoptosis and PARP is cleaved by caspase-3 before it can protect p53 from degradation. Destabilization of p53 by cleavage of PARP may be important in cell fate decision favoring apoptosis.
Asunto(s)
Apoptosis/fisiología , Células Cultivadas/efectos de la radiación , Poli Adenosina Difosfato Ribosa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Caspasa 3/metabolismo , Relación Dosis-Respuesta en la Radiación , Activación Enzimática , Humanos , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma , Proteína p53 Supresora de Tumor/genética , Rayos UltravioletaRESUMEN
BACKGROUND: Diabetics and experimental animal models exhibit high oxidative stress due to persistent and chronic hyperglycemia, thereby deplete the activity of the antioxidative defense system and thereby promote the generation of free radicals. The current study examined the effects of vitamin E on oxidative stress and membrane fluidity in the brain of diabetes-induced rats. METHODS: Sprague-Dawley male rats were randomly assigned to normal and streptozotocin (STZ)-induced diabetic groups. The diabetic groups were fed a vitamin E-free diet, 40 mg vitamin E/kg diet, or 400 mg vitamin E/kg diet. Diabetes was induced with STZ after 3 weeks of the experimental diet, then the rats were sacrificed 9 days later to determine the oxidative stress and cell membrane fluidity in the brain. RESULTS: Dietary vitamin E strengthened the antioxidative defense system with an increased activity of the antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and increased vitamin E content, in the brain of the diabetes-induced experimental rats. Accordingly, vitamin E was found to reduce the accumulation of reactive oxygen species (ROS), such as superoxide radical decrease the generation of oxidative damage substances, such as the carbonyl value, increase the membrane fluidity lowered by oxidative damage, and significantly improve the lipid composition. CONCLUSIONS: Vitamin E was found to be excellent for strengthening the antioxidative defense system, reducing the generation of ROS and damaging oxidative substances, and maintaining membrane fluidity in the brain of diabetes-induced rats.