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Title: | 探討AMPK在大鼠嗜鹼性白血病細胞株RBL-2H3調控FcεRI所誘導的訊息傳遞 AMPK regulation of FcεRI-mediated signal transduction in RBL-2H3 rat basophilic leukemia cells |
Authors: | Kai-Chun Lin 林凱君 |
Advisor: | 林琬琬(Wan-Wan Lin) |
Keyword: | 腺?磷酸活化激?,嗜鹼性白血球,高親和力免疫球蛋白E受體, AMPK,RBL-2H3,FcεRI,Lyn,Syk,Akt, |
Publication Year : | 2014 |
Degree: | 碩士 |
Abstract: | 5’-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a sensor of cellular and whole body energy homeostasis that coordinates metabolism pathway in order to balance energy supply with demand. Recently, many studies have revealed that AMPK activation exerts anti-inflammatory and anti-immunosuppressive effects through blunting the release of inflammatory mediators in a variety of cell types and models of inflammatory diseases. In allergic conditions, antigen-induced aggregation of high affinity IgE receptor, FcεRI, on mast cells has been demonstrated to use Lyn and/or Fyn kinase-dependent pathways to initiate a serious of activating signaling events. Although it is well known that AMPK exerts a negative effect on FcεRI-dependent mast cells signals and anaphylaxis through regulating downstream signal of Fyn, the precise regulation between Lyn, the major expressed Src family kinase (SFK) in mast cells and basophils, and AMPK in the context of FcεRI signaling has not been fully elucidated. In this study, we are interested to investigate whether AMPK plays a regulatory role in FcεRI-activated Lyn signaling in rat RBL-2H3 basophilic leukemia cells. As a result, we found that inhibitory AMPK phosphorylation at site Ser485/491 is increased upon FcεRI activation. Signaling cascade of Lyn-Syk-Akt mediates AMPK phosphorylation at Ser485/491, demonstrating that AMPK inhibition is downstream of FcεRI-activated Lyn signaling. Moreover, we showed that AMPK negatively regulates basophils activation and cytokine TNFα release through regulating protein interaction among FcεRI β and γ subunits and receptor proximal molecules, Lyn and Syk. Notably, RBL-2H3 cells predominantly express AMPKα2 isoform, whereas both AMPKα1 and α2 isoforms all participate in FcεRI β and/or γ subunits phosphorylation in vitro. The exact detailed molecular mechanism in this aspect needs further investigation in the future. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18459 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 藥理學科所 |
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ntu-103-1.pdf Restricted Access | 3.98 MB | Adobe PDF |
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