利用蛋白質體技術探討胱胺酸對紅斑性狼瘡之作用機制及相關治療標靶之開發

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 研究計劃 > Item 310902500/3234

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3234

Title:	利用蛋白質體技術探討胱胺酸對紅斑性狼瘡之作用機制及相關治療標靶之開發
Authors:	曾博修;徐再靜;蔡鈞州;林宗旻;蕭元超;唐于珺 Tzang, Bor-Show;Hsu, Tsai-Ching;Tsai, Chun-Chou;Lin, Tsung Ming;Hsiao, Yuan-Chao;Tang, Yu-Chun
Contributors:	中山醫學大學生化學科{生化科與生化暨生技研究所為科所合一}
Keywords:	系統性紅斑性狼瘡;胱胺;蛋白體學;調節型T細胞;治療標靶 Systemic lupus erythematosus (SLE);cystamine;therapeutic-target;regular T cells;proteomic
Date:	2010
Issue Date:	2010-12-16T03:47:34Z (UTC)
Abstract:	紅斑性狼瘡的致病原因目前仍未釐清，但最新研究相信是因為細胞凋亡的過程失衡﹐導致凋亡小體無法被正確辨認和清除﹐並使免疫耐受破壞而產生自體抗體﹐引起全身發炎反應。而胱胺是已知的殼胺醯胺轉移脢抑制劑﹐可以抑制凋亡相關的酵素活性和神經細胞的降解(degradation)﹐並已經應用在舞蹈症病人之臨床試驗上。而我們先前的研究中也發現﹐胱胺可以降低狼瘡小鼠血液中MMP-9的活性﹐使得細胞激素TNF-a及TGF-beta表現下降﹐更可以使得aCL自體抗體的效價減低。延續了胱胺對狼瘡小鼠之效益的研究﹐本研究計畫更進一步驗證了胱胺對狼瘡小鼠具有減緩全身性發炎效果﹐並能改善狼瘡小鼠巨嗜細胞凋亡的比例。並發現胱胺能提升狼瘡鼠抗氧化酵素Catalase, GSH活性及降低脂質裂解的情況。我們亦發現胱胺可以提高脾臟CD4+/CD25+ 調節型T細胞族群﹐進而有效改善狼瘡鼠之自體免疫特性。此外﹐我們也利用了蛋白質體技術﹐分析狼瘡鼠巨嗜細胞在處理胱胺前後之蛋白質點表現上的差異﹐並建立了雙向電泳的主圖樣。同時我們也確認了這些受到胱胺調節之蛋白質點的身份之後﹐利用資料庫及文獻搜尋比對﹐選定兩個治療標靶﹐並找到其相關調節之藥物﹐相信可作為未來臨床前試驗及人體試驗之重要參考。 The etiology and treatment of Systemic lupus erythematosus (SLE) are still unclear. However, the impaired clearance and accumulation of apoptotic bodies has been recognized as a major factor to induce inflammation, breakdown of immuno-tolerance, and production of autoantibodies. Cystamine is known as an inhibitor of transglutaminase 2 could inhibit the caspase activity and neuro-cell degeneration, which has been used in treatment with the animal model and human phase-I clinical trial of Huntington’s disease. Additionally, our recent study indicate the attenuated effects of cystamine on reducing the MMP-9 activity, expression of TNF-alpha and TGF-beta and aCL autoantibodies. To further investigate the effects of cystamine on SLE, this study has further identified the effects of cystamine on reducing the apoptosis macropahge in NZB/W F1 mice. Cystamine was also found to reduce the TBAR and increase the activity of serum catalase and GSH activity. On the other hand, the population of CD4+/CD25+ regular T cells was increased in spleen of NZB/W F1 mice that were treated with cystamine. Moreover, two-dimentional electrophoresis analysis was performed to analysis the peritoneal macrophages of NZB/W F1 mice that were received PBS or cystamine intravenously. The master 2-D-PAGE/image was performed and the protein spots with different expression level were picked, and identified by MALDI-TOF. In the meantime, we found two therapeutic targets and their regulatory compounds by database searching and literature review. In the future, we intend to repeat the animal experiments with these two compounds for verifying and confirming their effects on SLE.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3234
Appears in Collections:	[生化微生物免疫研究所] 研究計劃

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