Stress-activated protein kinase/c-Jun N-terminal kinase (JNK) plays a part in endothelin-1-induced vascular endothelial growth factor synthesis in osteoblasts.
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.
Wang
Xiaodan
X
Department of Pharmacology, Gifu University School of Medicine, Gifu, Japan.
Tokuda
Haruhiko
H
Hirade
Kouseki
K
Kozawa
Osamu
O
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001842:Bone and Bones / Q000166:cytology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000873:Anthracenes; D016228:Endothelial Growth Factors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580