STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells.
10.3858/emm.2009.41.2.012
- Author:
Hye Jin CHOI
1
;
Jung Han LEE
;
Shin Young PARK
;
Ju Hwan CHO
;
Joong Soo HAN
Author Information
1. Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea. jshan@hanyang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
extracellular signal-regulated MAP kinases;
phosphatidic acids;
phospholipases A2;
proto-oncogene proteins c-bcl-2;
STAT3 transcription factor
- MeSH:
Enzyme Inhibitors/pharmacology;
Gene Expression Regulation, Neoplastic;
Hela Cells;
Humans;
Mitogen-Activated Protein Kinase Kinases/genetics/metabolism;
Phosphatidic Acids/*genetics/metabolism;
Propranolol/pharmacology;
Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism;
Quinacrine/pharmacology;
RNA, Small Interfering/genetics;
STAT3 Transcription Factor/*genetics/metabolism
- From:Experimental & Molecular Medicine
2009;41(2):94-101
- CountryRepublic of Korea
- Language:English
-
Abstract:
Phosphatidic acid (PA), the product of a PLD-mediated reaction, is a lipid second messenger that participates in various intracellular signaling events and is known to regulate a growing list of signaling proteins. We found that Bcl-2 was upregulated by PA treatment in HeLa cells. However, how PA upregulates Bcl-2 expression has not yet been studied. In this study, we tried to discover the mechanisms of Bcl-2 up-regulation by PA treatment in HeLa cells. Treatment with PA resulted in significantly increased expression of Bcl-2 in HeLa cells. Moreover, PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of PLA2, but not by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Treatment of 1,2-dipalmitoryl-sn-glycero-3-phosphate (DPPA) also increased Bcl-2 expression. These results indicate that Bcl-2 expression is mediated by lysophosphatidic acid (LPA), not by arachidonic acid (AA). Thereafter, we used MEK1/2 inhibitor, PD98059 to investigate the relationship between ERK1/2 MAPK and PA-induced Bcl-2 expression. PA-induced Bcl-2 expression was decreased when ERK1/2 was inhibited by PD98059. The transcription factor such as STAT3 which is controlled by ERK1/2 MAPK was increased along with Bcl-2 expression when the cells were treated with PA. Furthermore, STAT3 siRNA treatments inhibited PA-induced Bcl-2 expression, suggesting that STAT3 (Ser727) is involved in PA-induced Bcl-2 expression. Taken together, these findings indicate that PA acts as an important mediator for increasing Bcl-2 expression through STAT3 (Ser727) activation via the ERK1/2 MAPK pathway.
