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研究生:沈煌偉
研究生(外文):Shen, Huang-Wei
論文名稱:前列腺環素致效劑對佛波脂引起HEL細胞分化之調控
論文名稱(外文):Regulation of phorbol ester induced human erythroleukemiacells differentiation by prostacyclin agonist
指導教授:簡偉明
指導教授(外文):Kan, Wai-Ming
口試委員:陳清玉錢偉鈞
口試委員(外文):Ching-Yuh ChernWei-Jyun Chien
口試日期:2010-07-10
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:93
中文關鍵詞:佛波酯前列腺素人類紅白血球細胞
外文關鍵詞:PMAprostacyclinHEL
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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 Rö318425 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.
Abstract 2
introduction 7
Materials and methods 23
Materials 23
Methods 26
Result 32
Discussion 52
References 62
Fingures 72
自述 93
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