title: (--)-epigallocatechin gallate enhances prostaglandin F2alpha-induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts.
abstract: Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F(2alpha) (PGF(2alpha)) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. To clarify the mechanism of catechin effect on osteoblasts, we investigated the effect of (--)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, on the VEGF synthesis by PGF(2alpha) in MC3T3-E1 cells. The PGF(2alpha)-induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 microM. EGCG did not affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase. SB203580, a specific inhibitor of p38 MAP kinase, and SP600125, a specific inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), reduced the PGF(2alpha)-induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF(2alpha) without affecting the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF(2alpha)-induced phosphorylation of c-Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF(2alpha)-stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts.
authors.affiliation: Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. tokuda@ncgg.go.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Hanai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ohta
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D015237:Dinoprost / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010120:Oxytocics; D011480:Protease Inhibitors; D016755:Proto-Oncogene Proteins c-jun; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; D015237:Dinoprost; C045651:epigallocatechin gallate; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases