Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene expression in astroglial cells via cPKC and ERK1/2 pathways independently.
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.
Yu
Hai
H
Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Oh-Hashi
Kentaro
K
Tanaka
Tatsuhide
T
Sai
Aihua
A
Inoue
Makoto
M
Hirata
Yoko
Y
Kiuchi
Kazutoshi
K
D000544:Alzheimer Disease; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000096:biosynthesis* / Q000235:genetics; D008516:Medicine, Chinese Traditional; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D032267:Rehmannia / Q000737:chemistry*; D015533:Transcriptional Activation
D004365:Drugs, Chinese Herbal; D051098:Glial Cell Line-Derived Neurotrophic Factors; D012333:RNA, Messenger; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3