Increased spermidine or spermine level is essential for hepatocyte growth factor-induced DNA synthesis in cultured rat hepatocytes.
OBJECTIVE
Hepatocyte growth factor is a potent mitogen for mature hepatocytes and seems to act as a trigger for liver regeneration. Hepatocyte growth factor was first purified from human and rabbit plasma and rat platelets. Additionally, putrescine, spermidine, and spermine are widely distributed in many different cells; intracellular concentrations of these polyamines are closely related to cell proliferation. The present study examined whether polyamine metabolism is involved in hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes.


METHODS
Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[1-14C]ornithine and S-adenosyl-L-[carboxyl-14C]methionine, respectively.


RESULTS
alpha-Difluoromethylornithine inhibited hepatocyte growth factor-induced DNA synthesis by only 21%. On the other hand, methylglyoxal bis(guanylhydrazone) completely inhibited hepatocyte growth factor-induced DNA synthesis to nontreated control level. The inhibitory effect of methylglyoxal bis(guanylhydrazone) on hepatocyte growth factor-induced DNA synthesis was reversed by exogenously added spermidine or spermine.


CONCLUSIONS
Spermidine or spermine is essential for hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes.
Higaki
I
I
Second Department of Biochemistry, Osaka City University Medical School, Japan.
Matsui-Yuasa
I
I
Terakura
M
M
Kinoshita
H
H
Otani
S
S
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D000518:Eflornithine / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008935:Mitoguazone / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000097:blood*; D013096:Spermine / Q000097:blood*
D065108:Ornithine Decarboxylase Inhibitors; D013096:Spermine; D017228:Hepatocyte Growth Factor; D004247:DNA; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D000518:Eflornithine