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Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes
Liu, Han1; Li, Hui1; Guo, Liyuan1; Li, Mengsen3; Li, Chaoying1; Wang, Shanshan1; Jiang, Wei1; Liu, Xinhua1; McNutt, Michael A.2; Li, Gang1
关键词Morphine Mu opioid receptor PI3K Signaling Gene expression Regulation
刊名BIOCHEMICAL PHARMACOLOGY
2010-02-01
DOI10.1016/j.bcp.2009.09.013
79期:3页:516-523
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]SIMIAN IMMUNODEFICIENCY VIRUS ; CEM X174 CELLS ; TRANSCRIPTIONAL REGULATION ; PHOSPHOINOSITIDE 3-KINASE ; PROMOTER REGION ; GENE-EXPRESSION ; IN-VITRO ; APOPTOSIS ; SURVIVAL ; ACTIVATION
英文摘要

Despite the substantial progress made in understanding initiation expression of the MOR gene in lymphocytes, the signal pathway associated with MOR gene transcription remains to be better defined. As the phosphatidylinositol 3-kinase (PI3K)/AKT pathway can mediate diverse biological responses and is crucial for optimal immune responses and lymphocyte development, this study was undertaken to delineate the role of PI3K/AKT signaling in expression of the MOR gene in CEM x 174 cells. The data show that morphine treatment enhanced the level of phosphorylated, rather than un-phosphorylated, PI3K and AKT, which were synchronously recruited to membrane. The levels of PTEN and p53 which are negative regulators of these signal molecules were reduced, and as a result, the interaction between PTEN and p53 was completely interrupted. With morphine treatment, the levels of both cytoplasmic and nuclear E2F1 which is the downstream effecter of AKT were elevated and the interaction of E2F1 with YY1, rather than Sp1, was also increased. Subsequently, E2F1 triggered the transcription of the MOR gene through its enhanced ability to bind the element in promoter region of the MOR gene. All responses to morphine were abolished by naloxone, which is an antagonist of MOR, or by LY294002, an inhibitor of PI3K, implying specific involvement of PI3K/AKT. These results strongly suggest that the PI3K/AKT pathway plays a critical role in the transfer of signal from morphine stimuli to the machinery by which MOR gene transcription is initiated. (C) 2009 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000273694900024
项目编号30621002 ; 30671856 ; 30772536 ; 20070001735
资助机构National Natural Science Foundation of China ; Foundation of National Education Ministry
引用统计
被引频次:21[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53257
专题北京大学基础医学院_病理学系
作者单位1.Hainan Med Coll, Key Lab Mol Biol, Haikou 570102, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China
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GB/T 7714
Liu, Han,Li, Hui,Guo, Liyuan,et al. Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes[J]. BIOCHEMICAL PHARMACOLOGY,2010,79(3):516-523.
APA Liu, Han.,Li, Hui.,Guo, Liyuan.,Li, Mengsen.,Li, Chaoying.,...&Li, Gang.(2010).Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes.BIOCHEMICAL PHARMACOLOGY,79(3),516-523.
MLA Liu, Han,et al."Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes".BIOCHEMICAL PHARMACOLOGY 79.3(2010):516-523.
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