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Sphingosine 1‐Phosphate Induces Heat Shock Protein 27 via p38 Mitogen‐Activated Protein Kinase Activation in Osteoblasts
Author(s) -
Kozawa Osamu,
Niwa Masayuki,
Matsuno Hiroyuki,
Tokuda Haruhiko,
Miwa Masaichi,
Ito Hidenori,
Kato Kanefusa,
Uematsu Toshihiko
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.10.1761
Subject(s) - sphingosine , sphingosine kinase 1 , sphingosine kinase , sphingosine 1 phosphate , kinase , hsp27 , protein kinase a , microbiology and biotechnology , map kinase kinase kinase , lipid signaling , biology , p38 mitogen activated protein kinases , ceramide , mitogen activated protein kinase kinase , chemistry , biochemistry , heat shock protein , hsp70 , enzyme , apoptosis , receptor , gene
We previously showed that sphingosine 1‐phosphate acts as a second messenger for tumor necrosis factor α–induced interleukin‐6 synthesis in osteoblast‐like MC3T3‐E1 cells and that the synthesis by sphingosine 1‐phosphate is dependent on p42/p44 mitogen‐activated protein (MAP) kinase activation. In the present study, we investigated the effect of sphingosine 1‐phosphate on the induction of heat shock protein 27 (HSP27) in MC3T3‐E1 cells. Not C 2 ‐ceramide, but sphingosine and sphingosine 1‐phosphate significantly induced HSP27 accumulation dose dependently in the range between 1μM and 30 μM. DL‐threo‐dihydrosphingosine, an inhibitor of sphingosine kinase, markedly inhibited the sphingosine‐induced HSP27 accumulation. Sphingosine 1‐phosphate induced increase in the levels of the mRNA for HSP27. Sphingosine 1‐phosphate stimulated the phosphorylation of p38 MAP kinase. The sphingosine 1‐phosphate–induced HSP27 accumulation was dose dependently suppressed by SB203580, an inhibitor of p38 MAP kinase, but not PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. SB203580 reduced the sphingosine 1‐phosphate–induced increase of mRNA for HSP27. These results strongly suggest that sphingosine 1‐phosphate–stimulated HSP27 induction is mediated via p38 MAP kinase activation in osteoblasts.