Signal transduction mechanism leading to enhanced proliferation of primary cultured adult XXXX hepatocytes treated with royal jelly 57-kDa protein.

@entity670 @entity4286 @entity2307 @entity7131 @entity5597 @entity3446 @entity4385 @entity35 @entity669
A 57-kDa protein in royal jelly (RJ) was previously shown to stimulate hepatocyte DNA synthesis and prolongs the proliferation of hepatocytes as well as increasing albumin production [Kamakura, M., Suenobu, N., and Fukushima, M. (2001) Biochem. Biophys. Res. Commun. 282, 865-874]. In this study, I investigated the signal transduction mechanisms involved in the induction of hepatocyte DNA synthesis and the promotion of cell survival by this 57-kDa protein in primary cultures of adult @entity35 hepatocytes. Hepatocyte DNA synthesis induced by the 57-kDa protein was not influenced by several alpha- and beta-adrenoceptor antagonists, but was dose-dependently abolished by an inhibitor of a @entity669 -specific protein kinase, @entity670 . A phospholipase C inhibitor ( @entity4385 ) and a @entity7131 ( @entity7131 ) inhibitor ( @entity5597 ) inhibited 57-kDa protein-stimulated he-patocyte DNA synthesis, whereas a protein kinase A inhibitor (H-89) did not. The 57-kDa protein also activated @entity7131 in @entity35 hepatocytes. Various inhibitors of intracellular signal transduction elements ( @entity4286 , p21 ras farnesyltransferase inhibitor, @entity2307 and @entity3446 ) also blocked hepatocyte DNA synthesis induced by the 57-kDa protein. Furthermore, the 57-kDa protein activated mitogen-activated protein (MAP) kinase in @entity35 hepatocytes. The activation of MAP kinase by the 57-kDa protein was inhibited by @entity4286 and @entity5597 . The 57-kDa protein also activated protein kinase B, which is a key regulator of cell survival. These results suggest that, like growth factors, the 57-kDa protein activates several important intracellular signaling factors involved in the stimulation of hepatocyte DNA synthesis and the protection of cells from apoptosis.
