(-)-epigallocatechin gallate inhibits prostaglandin D2-stimulated HSP27 induction via suppression of the p44/p42 MAP kinase pathway in osteoblasts.
We previously reported that prostaglandin D2 (PGD2) stimulates heat shock protein 27 (HSP27) induction through p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), the major polyphenol found in green tea, affects the induction of HSP27 in these cells and the mechanism. EGCG significantly reduced the HSP27 induction stimulated by PGD2 without affecting the levels of HSP70. The PGD2-induced phosphorylation of p38 MAP kinase or SAPK/JNK was not affected by EGCG. On the contrary, EGCG markedly suppressed the PGD2-induced phosphorylation of p44/p42 MAP kinase and MEK1/2. However, the PGD2-induced phosphorylation of Raf-1 was not inhibited by EGCG. These results strongly suggest that EGCG suppresses the PGD2-stimulated induction of HSP27 at the point between Raf-1 and MEK1/2 in osteoblasts.
Yamauchi
Junichi
J
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Takai
Shinji
S
Matsushima-Nishiwaki
Rie
R
Hanai
Yoshiteru
Y
Doi
Tomoaki
T
Kato
Hisaaki
H
Ogura
Shinji
S
Kato
Kanefusa
K
Tokuda
Haruhiko
H
Kozawa
Osamu
O
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048730:MAP Kinase Kinase Kinase 2 / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D048730:MAP Kinase Kinase Kinase 2; C482619:Map3k2 protein, mouse; D048369:MAP Kinase Kinase 1; D015230:Prostaglandin D2