AMP-activated protein kinase positively regulates FGF-2-stimulated VEGF synthesis in osteoblasts

被引:20
作者
Kato, Kenji [1 ,2 ]
Tokuda, Haruhiko [1 ,3 ]
Adachi, Seiji [1 ]
Matsushima-Nishiwaki, Rie [1 ]
Natsume, Hideo [1 ,2 ]
Yamakawa, Kengo [1 ]
Gu, Yumi [1 ]
Otsuka, Takanobu [2 ]
Kozawa, Osamu [1 ]
机构
[1] Gifu Univ, Grad Sch Med, Dept Pharmacol, Gifu 5011194, Japan
[2] Nagoya City Univ, Grad Sch Med Sci, Dept Orthoped Surg, Nagoya, Aichi 4678601, Japan
[3] Natl Ctr Geriatr & Gerontol, Dept Clin Lab, Aichi 4748511, Japan
关键词
AMPK; FGF-2; VEGF; Osteoblast; GROWTH-FACTOR RELEASE; CYCLIC-AMP; RAT-LIVER; MODULATION; DIFFERENTIATION; EXPRESSION; STRESS;
D O I
10.1016/j.bbrc.2010.08.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
AMP-activated protein kinase (AMPK) is recognized as a regulator of energy homeostasis. We have previously reported that basic fibroblast growth factor (FGF-2) stimulates vascular endothelial growth factor (VEGF) release through the activation of p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of AMPK in FGF-2-stimulated VEGF release in these cells. FGF-2 time-dependently induced the phosphorylation of AMPK alpha-subunit (Thr-172). Compound C, an AMPK inhibitor, which suppressed the FGF-2-induced phosphorylation of AMPK, significantly inhibited the VEGF release stimulated by FGF-2. The AMPK inhibitor also reduced the mRNA expression of VEGF induced by FGF-2. The FGF-2-induced phosphorylation of both p44/p42 MAP kinase and SAPK/JNK was attenuated by compound C. These results strongly suggest that AMPK positively regulates the FGF-2-stimulated VEGF synthesis via p44/p42 MAP kinase and SAPK/JNK in osteoblasts. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:123 / 127
页数:5
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