Fifty-seven-kDa protein in royal jelly enhances proliferation of primary cultured rat hepatocytes and increases albumin production in the absence of serum

We have previously shown that 57-kDa protein in royal jelly (RJ) was specifically degraded in proportion to both storage temperature and storage period, and we suggested that it could be useful as a marker of freshness of RJ (Kamakura, M., Fukuda, T., Fukushima, M, and Yonekura, M. (2001) Biosci. Biotechnol. Biochem. 65, 277-284,), Here, we investigated the physiological effects of 57-kDa protein on primary cultured rat hepatocytes in the absence of serum. The 57-kDa protein and RJ significantly stimulated hepatocyte DNA synthesis, whereas bovine serum albumin and RJ stored at 40 degreesC for 7 days, which lacks 57-kDa protein, did not. The mitogenic activity of 57-kDa protein was lost after treatment with trypsin. These results indicate that 57-kDa protein acts as a mitogen. The stimulatory effect of 57-kDa protein was dose-dependent and was more potent at lower than at higher cell densities. The 57-kDa protein also prolonged the cell proliferation of primary cultured rat hepatocytes, with an enhancement of albumin production compared to untreated cells. Therefore, 57-kDa protein is likely to promote liver regeneration and may have a cytoprotective action on hepatocytes. (C) 2001 Academic Press.