Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene expression in astroglial cells via cPKC and ERK1/2 pathways independently

Abstract

Among four herbs of traditional Chinese medicines (TCMs) used in the therapy of dementia, Rehmannia glutinosa (RG) was found to induce the gene expression of glial cell line-derived neurotrophic factor (GDNF) in C6 glioblastoma cells and primary cultured astrocytes. The RG-induced GDNF mRNA up-regulation in C6 glioblastoma cells was completely attenuated by the presence of a pan-specific protein kinase C (PKC) inhibitor (Ro-31-8220) and a MAPK/ERK kinase 1 (MEK1) inhibitor (U0126). A conventional PKC inhibitor (Gö6976) also significantly decreased GDNF gene induction. On the other hand, RG treatment was found to stimulate phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), which preceded GDNF mRNA induction in C6 glioblastoma cells. However, none of the PKC inhibitors significantly changed RG-stimulated ERK1/2 phosphorylation. Therefore, RG-stimulated GDNF gene expression could be independently up-regulated through cPKC and ERK 1/2 pathways in C6 glioblastoma cells.