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(−)‐epigallocatechin gallate enhances prostaglandin F 2α ‐induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts
Author(s) -
Tokuda Haruhiko,
Takai Shinji,
MatsushimaNishiwaki Rie,
Akamatsu Shigeru,
Hanai Yoshiteru,
Hosoi Takayuki,
Harada Atsushi,
Ohta Toshiki,
Kozawa Osamu
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21104
Subject(s) - p38 mitogen activated protein kinases , chemistry , kinase , mitogen activated protein kinase , protein kinase a , phosphorylation , osteoblast , microbiology and biotechnology , gallate , protein kinase c , biochemistry , biology , nuclear chemistry , in vitro
Abstract Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F 2α (PGF 2α ) 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 2α in MC3T3‐E1 cells. The PGF 2α ‐induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 µM. EGCG did not affect the PGF 2α ‐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 2α ‐induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF 2α without affecting the PGF 2α ‐induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF 2α ‐induced phosphorylation of c‐Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF 2α ‐stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts. J. Cell. Biochem. 100: 1146–1153, 2007. © 2006 Wiley‐Liss, Inc.