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.
机构:
Hanyang Univ, Biomed Res Inst, Coll Med, Seoul 133791, South Korea
Hanyang Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 133791, South KoreaHanyang Univ, Biomed Res Inst, Coll Med, Seoul 133791, South Korea
Choi, Hye-Jin
Chang, Brian Junho
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Univ Calif San Diego, John Muir Coll, San Diego, CA 92092 USAHanyang Univ, Biomed Res Inst, Coll Med, Seoul 133791, South Korea
Chang, Brian Junho
Han, Joong-Soo
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Hanyang Univ, Biomed Res Inst, Coll Med, Seoul 133791, South Korea
Hanyang Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 133791, South KoreaHanyang Univ, Biomed Res Inst, Coll Med, Seoul 133791, South Korea
机构:
Hanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Yoon, Sung Nyo
Kim, Kang Sik
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Hanyang Univ, Coll Med, Dept Surg, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Kim, Kang Sik
Cho, Ju Hwan
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Hanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Cho, Ju Hwan
Ma, Weina
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Hanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Ma, Weina
Choi, Hye-Jin
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Hanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Choi, Hye-Jin
Kwon, Sung-Joon
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Hanyang Univ, Coll Med, Dept Surg, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Kwon, Sung-Joon
Han, Joong-Soo
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Hanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Biomed Res Inst, Seoul 133791, South Korea
机构:
Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Oh, Doo-Yi
Cho, Ju Hwan
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Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Cho, Ju Hwan
Park, Shin-Young
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Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Park, Shin-Young
Kim, Yong Seok
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Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Kim, Yong Seok
Yoon, Young-Ju
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Catholic Univ, Coll Med, Dept Physiol, Seoul, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Yoon, Young-Ju
Yoon, Shin Hee
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Catholic Univ, Coll Med, Dept Physiol, Seoul, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Yoon, Shin Hee
Chung, Kwang Chul
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Yonsei Univ, Coll Sci, Dept Biol, Seoul, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Chung, Kwang Chul
Lee, Ki Sung
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PaiChai Univ, Res Ctr Biomed Resources, Taejon, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Lee, Ki Sung
Han, Joong-Soo
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Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South Korea
PaiChai Univ, Res Ctr Biomed Resources, Taejon, South KoreaHanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea