title: Phospholipase D1 is an important regulator of bFGF-induced neurotrophin-3 expression and neurite outgrowth in H19-7 cells.
abstract: The purpose of this study was to examine the role of phospholipase D1 (PLD1) in basic fibroblast growth factor (bFGF)-induced neurotrophin-3 (NT-3) expression and neurite outgrowth in H19-7 rat hippocampal neuronal progenitor cells. Overexpression of PLD1 increased bFGF-induced NT-3 expression, and dominant-negative-PLD1 or PLD1 siRNA abolished bFGF-induced NT-3 expression and neurite outgrowth. Treatment with bFGF activated the RhoA/Rho-associated kinase (ROCK)/c-jun N-terminal kinase (JNK) pathway, and bFGF-induced NT-3 expression was blocked by a dominant-negative RhoA as well as by a specific Rho-kinase inhibitor (Y27632) and a SAPK/JNK inhibitor (SP600125). Furthermore, bFGF-induced JNK activation was also blocked by Y27632. These results indicate that the RhoA/ROCK/JNK pathway acts as an upstream signaling pathway in bFGF-induced NT-3 expression. Also, phosphatidic acid, the product of PLD, increased NT-3 expression. We found that PLD regulated the RhoA/ROCK/JNK pathway, which then led to Elk-1 transactivation. When Elk-1 activity was blocked by Elk-1 siRNA, bFGF-induced NT-3 expression and neurite outgrowth decreased. NT-3 overexpression increased neurite outgrowth, indicating that NT-3 is important for neurite outgrowth. Taken together, these results suggest that PLD1 is an important regulator of bFGF-induced NT-3 expression and neurite outgrowth, which are mediated by the RhoA/ROCK/JNK pathway via Elk-1 in H19-7 cells.
authors.affiliation: Biomedical Research Institute and Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul, 133-791, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Brian Junho
authors.initials: BJ
authors.lastname: Chang
authors.forename: Joong-Soo
authors.initials: JS
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D016501:Neurites / Q000187:drug effects / Q000201:enzymology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020933:Neurotrophin 3; D010712:Phosphatidic Acids; D050807:ets-Domain Protein Elk-1; D016222:Fibroblast Growth Factor 2; D054460:rho-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D010739:Phospholipase D; C106801:phospholipase D1; D020742:rhoA GTP-Binding Protein