title: Induction of Bcl-xL is a possible mechanism of anti-apoptotic effect by prostaglandin E2 EP4-receptor agonist in human hepatocellular carcinoma HepG2 cells.
abstract: Because fulminant hepatic failure has a poor prognosis without liver transplantation, it is required to develop new therapies directed toward hepatocyte protection and regeneration. Previously, we showed the anti-apoptotic effects of a prostaglandin E2 EP4-receptor agonist (PGE2R-A) in a rat model of acute liver failure. The aim of this study is to determine the anti-apoptotic mechanism underlying the hepatocyte protective effect of PGE2R-A in vitro. Method: (1) Apoptosis was induced in HepG2 cells using CH11, an agonistic anti-Fas antibody. The apoptosis index (percentage of apoptotic cells with respect to the total number of cells) was sequentially estimated after the administration of CH11 alone or CH11 together with indomethacin or PGE2R-A (ONO-AE1-437). (2) The expression levels of Bcl-xL and Mcl-1, members of the anti-apoptotic Bcl-2 family, were sequentially determined by western blot analysis after treatment with PGE2R-A. Results: (1) Apoptosis indexes 6h after treatment with CH11 alone, CH11 plus indomethacin, and CH11 plus PGE2R-A were 24, 42, and 16%, respectively. (2) The expression level of the Bcl-xL protein and mRNA significantly increased 30-180min after treatment with PGE2R-A, while indomethacin decreased the expression levels of Mcl-1 proteins. Conclusion: Direct induction of Bcl-xL plays an important role in the hepatocyte protective effects induced by PGE2R-A.
authors.affiliation: First Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ushio
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takikawa
authors.forename: Shi De
authors.initials: SD
authors.lastname: Lin
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki