RESUMEN
In rat hippocampus, kainic acid (KA; 10 mg/kg; i.p.) increased the phosphorylated forms of ERK1/2 (p-ERK1/2) and Jun kinase1 (p-JNK1), but not p-JNK2 and p38 (p-p38). The preadministration with cycloheximide (CHX; 5 mg/kg; i.p.) inhibited KA-induced increase of p-JNK1, but not p-ERK1/2. Surprisingly, the phosphorylated upstream MAP kinase kinases (p-MKKs) were not correlated with their downstream MAP kinases. The basal p-MKK1/2 levels were completely abolished by KA, which were reversed by CHX. In addition, p-MKK4 and p-MKK3/6 levels were enhanced by CHX alone, but were attenuated by KA. Thus, our results showed that KA increased the p-ERK and p-JNK levels in rat hippocampus, which were not parallel with their classical upstreamal kinases.
Asunto(s)
Animales , Ratas , Cicloheximida , Hipocampo , Ácido Kaínico , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Quinasas Activadas por Mitógenos , Fosforilación , FosfotransferasasRESUMEN
We have studied the effects of excitatory amino acids on the expression of the c-fos and c-jun mRNA in rat C6 glioma cells. The glutamate, N-methyl-D-aspartate (NMDA), and kainic acid (KA) increased c-fos mRNA level in a concentration-dependent manner. However, they did not affect c-jun mRNA level. In addition, forskolin and phorbol 12-myristate 13-acetate (PMA) increased c-fos mRNA level. Furthermore, PMA increased c-jun mRNA level whereas forskolin downregulated c-jun mRNA level. The glutamate, NMDA and KA, at a concentration of 0.25 mM, did not affect the basal c-fos and c-jun mRNA levels, and also did not affect forskolin- and PMA-induced responses. Furthermore, both forskolin and PMA itself increased the phosphorylation of ERK (extracellular signal regulated kinase) and CREB (cyclicAMP responsible element binding protein) proteins. The KA, NMDA, and glutamate did not affect forskolin-induced increase of ERK and CREB phosphorylation. The KA decreased PMA-induced increase of phosphorylation of ERK and CREB proteins, whereas glutamate and NMDA did not affect the phosphorylation of ERK and CREB proteins induced by PMA. These findings suggest that, in C6 glioma cells, c-fos mRNA induction induced by EAAs is not mediated by phosphorylation of ERK and CREB proteins.
Asunto(s)
Animales , Ratas , Colforsina , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Aminoácidos Excitadores , Expresión Génica , Glioma , Ácido Glutámico , Ácido Kaínico , N-Metilaspartato , Fosforilación , Receptores de Glutamato , ARN MensajeroRESUMEN
No Abstract Available.