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Intracellular calcium as a second messenger for human hepatocyte growth factor in hepatocytes
Author(s) -
Kaneko Akira,
Hayashi Norio,
Tsubouchi Hirohito,
Tanaka Yuji,
Ito Toshifumi,
Sasaki Yutaka,
Fusamoto Hideyuki,
Daikuhara Yasushi,
Kamada Takenobu
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150632
Subject(s) - hepatocyte , intracellular , hepatocyte growth factor , growth factor , biology , endocrinology , medicine , calcium in biology , cell culture , dna synthesis , second messenger system , cell growth , microbiology and biotechnology , in vitro , receptor , biochemistry , genetics
Human hepatocyte growth factor is a newly discovered substance that stimulates DNA synthesis in vitro. In this study, we examined intracellular Ca 2+ movement as one of the second messengers for human hepatocyte growth factor in primary‐cultured hepatocytes. The addition of hHGF induced Ca 2+ oscillation, but the frequency of oscillations varied from cell to cell. We also saw marked intercellular heterogeneity in the initial latent period for the Ca 2+ response; the mean latent period was rather longer than those seen with phenylephrine and vasopressin. This difference in the initial latent period may be due to the difference in the pathways of Ca 2+ elevation. Duration of culture determined the number of human hepatocyte growth factor—responsive cells; their number peaked at 2 to 5 hours of confluent culture, whereas the peak was earlier in a low‐density culture. These changes in responsiveness during culture can be explained by the cell cycle—dependent sensitivity to human hepatocyte growth factor of hepatocytes. The Ca 2+ response to human hepatocyte growth factor was dose dependent; 10 −10 mol/L hHGF gave the highest Ca 2+ response, similar to the dose‐response curve of DNA synthesis. We even observed the Ca 2+ response in the Ca 2+ ‐free buffer, so the increase in Ca 2+ was considered due to release from intracellular Ca 2+ stores. These results suggest that human hepatocyte growth factor causes the intracellular Ca 2+ elevation in the early stage of the cell cycle and that it plays important roles in the signal transduction systems for human hepatocyte growth factor and the proliferation of hepatocytes. (H EPATOLOGY 1992;15:1173–1178).