Enhancement by HSP90 inhibitor of PGD2-stimulated HSP27 induction in osteoblasts: suppression of SAPK/JNK and p38 MAP kinase

Publication date: Available online 1 April 2019Source: Prostaglandins & Other Lipid MediatorsAuthor(s): Woo Kim, Haruhiko Tokuda, Tetsu Kawabata, Kazuhiko Fujita, Go Sakai, Daiki Nakashima, Junko Tachi, Gen Kuroyanagi, Rie Matsushima-Nishiwaki, Kumiko Tanabe, Takanobu Otsuka, Hiroki Iida, Osamu KozawaAbstractHeat shock protein (HSP) 90 that is ubiquitously expressed in various tissues, is a major molecular chaperone. We have previously demonstrated that prostaglandin D2 (PGD2), a bone remodeling factor, elicits the expression of HSP27, a small HSP, through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of HSP90 in the PGD2-stimulated HSP27 induction and the underlying mechanism in MC3T3-E1 cells. Onalespib, an inhibitor of HSP90, significantly enhanced the PGD2-stimulated HSP27 induction. In addition, geldanamycin, another HSP90 inhibitor, potentiated the HSP27 induction. Both onalespib and geldanamycin markedly amplified the PGD2-induced phosphorylation of SAPK/JNK and p38 MAP kinase. SP600125, an inhibitor of SAPK/JNK, and SB203580, an inhibitor of p38 MAP kinase, suppressed the amplification by onalespib of the PGD2-stimulated HSP27 induction. These results strongly suggest that HSP90 plays a negative role in the HSP27 induction stimulated by PGD2 in osteoblasts, and that the inhibitory effect of HSP90 is mediated throu...

Source: Prostaglandins and Other Lipid Mediators - April 2, 2019 Category: Lipidology Source Type: research