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STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells
Experimental & Molecular Medicine ; : 94-101, 2009.
Article in English | WPRIM | ID: wpr-103079
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphatidic Acids / Propranolol / Quinacrine / HeLa Cells / Gene Expression Regulation, Neoplastic / Proto-Oncogene Proteins c-bcl-2 / Mitogen-Activated Protein Kinase Kinases / RNA, Small Interfering / Enzyme Inhibitors / STAT3 Transcription Factor Limits: Humans Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphatidic Acids / Propranolol / Quinacrine / HeLa Cells / Gene Expression Regulation, Neoplastic / Proto-Oncogene Proteins c-bcl-2 / Mitogen-Activated Protein Kinase Kinases / RNA, Small Interfering / Enzyme Inhibitors / STAT3 Transcription Factor Limits: Humans Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article