Stress-activated protein kinase/c-Jun N-terminal kinase (JNK) plays a part in endothelin-1-induced vascular endothelial growth factor synthesis in osteoblasts
✍ Scribed by Xiaodan Wang; Haruhiko Tokuda; Kouseki Hirade; Osamu Kozawa
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 166 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
We previously reported that endothelin‐1 (ET‐1) activates both p44/p42 mitogen‐activated protein (MAP) kinase and p38 MAP kinase in osteoblast‐like MC3T3‐E1 cells, and that not p44/p42 MAP kinase but p38 MAP kinase participates in the ET‐1‐induced vascular endothelial growth factor (VEGF) synthesis. In the present study, we investigated the involvement of stress‐activated protein kinase/c‐Jun N‐terminal kinase (JNK) in ET‐1‐induced VEGF synthesis in these cells. ET‐1 significantly induced the phosphorylation of JNK in a dose‐dependent manner in the range between 0.1 and 100 nM. SP600125, an inhibitor of JNK, markedly reduced the ET‐1‐induced VEGF synthesis. A combination of SP600125 and SB203580 additively reduced the ET‐1‐stimulated VEGF synthesis. SP600125 suppressed the ET‐1‐induced phosphorylation of JNK, while having no effect on the phosphorylation of p38 MAP kinase elicited by ET‐1. SB203580, an inhibitor of p38 MAP kinase, hardly affected the ET‐1‐induced phosphorylation of JNK. These results strongly suggest that JNK plays a role in ET‐1‐induced VEGF synthesis in addition to p38 MAP kinase in osteoblasts. J. Cell. Biochem. 87: 417–423, 2002. © 2002 Wiley‐Liss, Inc.