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.
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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