Phospholipase D1 mediates bFGF-induced Bcl-2 expression leading to neurite outgrowth in H19-7 cells
- Authors
- Yoon, Sung Nyo; Kim, Kang Sik; Cho, Ju Hwan; Ma, Weina; Choi, Hye-Jin; Kwon, Sung-Joon; Han, Joong-Soo
- Issue Date
- Jan-2012
- Publisher
- PORTLAND PRESS LTD
- Keywords
- Bcl-2; c-Jun N-terminal kinase (JNK); phospholipase C gamma (PLC gamma); phospholipase D1 (PLD1); Ras; signal transducer and activator of transcription 3 (STAT3)
- Citation
- BIOCHEMICAL JOURNAL, v.441, no.1, pp.407 - 416
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL JOURNAL
- Volume
- 441
- Number
- 1
- Start Page
- 407
- End Page
- 416
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/166525
- DOI
- 10.1042/BJ20110302
- ISSN
- 0264-6021
- Abstract
- The purpose of the present study was to investigate the role of PLD (phospholipase D) in bFGF (basic fibroblast growth factor)induced Bcl-2 expression and to examine whether overexpressed Bcl-2 influences neurite outgrowth in immortalized hippocampal progenitor cells (H19-7 cells). We found that Bcl-2 expression was maximally induced by bFGF within 24 h, and that this effect was reduced by inhibiting PLD1 expression with PLD1 small interfering RNA or by overexpressing DN (dominant-negative)-PLD1, whereas PLD1 overexpression markedly induced Bcl-2 expression. bFGF treatment activated Ras, Src, PI3K (phosphoinositide 3-kinase), PLC gamma (phospholipase C gamma) and PKC alpha (protein kinase C alpha). Among these molecules, Src and PKC alpha were not required for Bcl-2 expression. PLD activity was decreased by Ras. PI3K or PLC gamma inhibitor, suggesting that PLD1 activation occurred through Ras, PI3K or PLC gamma. We found that Ras was the most upstream molecule among these proteins, followed by the PI3K/PLC gamma pathway, indicating that bFGF-induced PLD activation took place through the Ras/PI3K/PLC gamma pathway. Furthermore, PLD1 was required for activation of JNK (c-Jun N-terminal kinase), which led to activation of STAT3 (signal transducer and activator of transcription 3) and finally Bcl-2 expression. When Bcl-2 was overexpressed, neurite outgrowth was stimulated along with induction of neurotrophic factors such as brain-derived neurotrophic factor and neurotrophin 4/5. In conclusion, PLD1 acts as a downstream effector of bFGF/Ras/PI3K/PLC gamma signalling and regulates Bcl-2 expression through JNK/STAT3, which leads to neurite outgrowth in H19-7 cells.
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