STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cellsopen access
- Authors
- Choi, Hye-Jin; Lee, Jung Han; Park, Shin-Young; Cho, Ju Hwan; Han, Joong-Soo
- Issue Date
- Feb-2009
- Publisher
- SPRINGERNATURE
- Keywords
- extracellular signal-regulated MAP kinases; phosphatidic acids; phospholipases A2; proto-oncogene proteins c-bcl-2; STAT3 transcription factor
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.41, no.2, pp.94 - 101
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 41
- Number
- 2
- Start Page
- 94
- End Page
- 101
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/177342
- DOI
- 10.3858/emm.2009.41.2.012
- ISSN
- 1226-3613
- 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 PLA(2), 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 (Ser(727)) 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 (Ser(727)) activation via the ERK1/2 MAPK pathway.
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