| 17482686 |
Kawao N, Okada K, Kawata S, Okamoto C, Tsuritani M, Ueshima S, Matsuo O: Plasmin decreases the BH3-only protein BimEL via the ERK1/2 signaling pathway in hepatocytes. Biochim Biophys Acta. 2007 Jun;1773(6):718-27. Epub 2007 Apr 1.
Since the signal transduction mechanisms responsible for liver regeneration mediated by the plasminogen/plasmin system remain largely undetermined, we have investigated whether plasmin regulates the pro-apoptotic protein Bim (EL) in primary hepatocytes. Plasmin bound to hepatocytes in part via its lysine binding sites (LBS). Plasmin also triggered phosphorylation of ERK1/2 without cell detachment. The plasmin-induced phosphorylation of ERK1/2 was inhibited by the LBS inhibitor epsilon-aminocaproic acid (EACA), the serine protease inhibitor aprotinin, and the MEK inhibitor PD98059. DFP-inactivated plasmin failed to phosphorylate ERK1/2. Plasmin temporally decreased the starvation-induced expression of Bim (EL) and activation of caspase-3 via the ERK1/2 signaling pathway, resulting in an enhancement of cell survival. The amount of mRNA for Bim increased 1 day after the injection of CCl (4) in livers of plasminogen knockout (Plg-KO) and the wild-type (WT) mice. The increase in Bim (EL) protein persisted for at least 7 days post-injection in livers of Plg-KO mice, whereas WT mice showed an increase in Bim (EL) protein 1 day after the injection. Plg-KO and WT mice showed notable phosphorylation of ERK1/2 7 and 3 days after the injection of CCl (4), respectively. Our data suggest that the plasminogen/plasmin system could decrease Bim (EL) expression via the ERK1/2 signaling pathway during liver regeneration. |
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