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Ethanolamine is a co‐mitogenic factor for proliferation of primary hepatocytes
Author(s) -
Ajioka Itsuki,
Akaike Toshihiro,
Watanabe Yoshifumi
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10012
Subject(s) - microbiology and biotechnology , cell cycle , dna synthesis , cell growth , cyclin d , cyclin a , hepatocyte growth factor , cyclin b , biology , chemistry , cyclin d1 , cell , biochemistry , receptor , dna
Mature adult parenchymal hepatocytes can enter the S phase in the presence of growth factors such as HGF and EGF, but rarely proliferate in culture. We hypothesized that the cell cycle of hepatocytes in culture is restricted before G 2 /M phase and we attempted to identify the factor that induces cell cycle progression. We found that the conditioned medium from long‐term cultured hepatocytes contained co‐mitogenic activity with other growth factors, which was attributed to ethanolamine (Etn). Etn induced not only DNA synthesis but also cell replication of cultured hepatocytes with various other growth factors. Etn and HGF synergistically induced cyclin D 1 , A and B expression, however, only cyclin B but not cyclin A formed a complex with Cdc2. In addition, Etn combined with HGF enhanced PKCβII expression and translocated PKCβII to the plasma membrane, and induced filopodia formation, which was inhibited by an antisense oligonucleotide against PKCβII. In addition, blocking the cytoskeleton rearrangement with inhibitors (colchicine, cytochalasin D, or chlerythrine (a specific PKC inhibitor)) inhibited cyclin expression and cell proliferation. Although Etn enhanced the downstream product, cellular phosphatidylethanolamine (PE), PE itself did not show any Etn‐like activities on hepatocytes. Taken together, our results indicate that Etn functions as a co‐replication factor to promote the cell cycle of mature hepatocytes to G 2 /M phase in the presence of growth factors. The activity is thought to be mediated by PKCβII‐dependent cyclin B expression. J. Cell. Biochem. 84: 249–263, 2002. © 2001 Wiley‐Liss, Inc.