| Summary: | 博士 === 國立成功大學 === 藥理學研究所 === 98 === Prostacyclin (PGI2), a major product of cyclooxygenase, exerts its function by binding to cell membrane specific prostacyclin receptor (IPR) and has been implicated in modulation of cardiovascular disorders. The present study examined a new function of IP receptor in regulation of hematopoietic cells differentiation in a PMA-stimulated HEL cell line model. HEL cells were pretreated with phorbol-diesters (PMA) for 24 hours and used as a model system. While treatment of PMA-stimulated HEL cells with IP agonists (beraprost or BMY45778) induced a dendrite-like morphology and attenuated megakaryocyte characteristics (megakaryocyte specific cell markers, enlargement of cytoplasmic mass and polyploidization). The display of dendrite-like morphology induced by IP agonists were blocked by MEK inhibitors. IP agonists also induced ERK1/2 activation, and were inhibited by pretreatment with IP antagonist Ro1138452 and PKC inhibitors GF109203x and R?318425 but not PKA or PI3K inhibitors. . Further study also found an induction of PKC-δ activation and inhibition of εPKC expression by IP receptor. The ERK1/2 and PKC-δ activation induced by beraprost also inhibited by specific PKC-δ inhibitor, rottlerin. Taken together, these results indicated an involvement of PKC-δ dependent ERK1/2 activation signaling pathway in IP receptor modulated PMA-treated HEL cells differentiation.
|
|---|
