title: PI3-Kinase Inhibitor LY294002 Repressed the Expression of Thrombin-Activatable Fibrinolysis Inhibitor in Human Hepatoma HepG2 Cells.
abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme biosynthesized in the liver and released into the blood circulation. Activated TAFI (TAFIa) has been implicated as an important player in maintaining the balance between blood coagulation and fibrinolysis. In the present study, regulation of TAFI (CPB2) gene expression was investigated using cultured human hepatoma HepG2 cells. HepG2 cells were treated with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the levels of TAFI antigen and CPB2 mRNA were measured. HepG2 cells treated with LY29400 decreased their release of TAFI antigen into the conditioned medium (CM). In parallel, there were decreased levels of CPB2 mRNA and TAFI antigen in the cells. However, CPB2 gene promoter activity was not influenced by treatment of the cells with LY294002. The half-life of the CPB2 transcript was shortened by treatment with LY294002 compared with control. The present results suggest that the PI3K inhibitor LY294002 suppresses expression of TAFI, a prothrombotic factor, by decreasing the stability of CPB2 transcripts.
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.forename: Jun
authors.initials: J
authors.lastname: Yazawa
authors.forename: Yuuka
authors.initials: Y
authors.lastname: Makino
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Takada
mesh_terms: D025901:Carboxypeptidase B2 / Q000235:genetics*; D002867:Chromones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C585364:CPB2 protein, human; D025901:Carboxypeptidase B2