哮喘大鼠肺T 細胞中組蛋白去乙酰基酶1 的表達及對組蛋白修飾的影響_《中國呼吸與危重監護雜志》

作者：

李成業 , 郭雪君 , 甘麗杏 , 丁濤 , 顧問

上海交通大學醫學院附屬新華醫院呼吸科( 上海 200092)通訊作者: 郭雪君, E-mail: guoxjz@ yahoo. com. cn;

關鍵詞：

哮喘 T 細胞組蛋白去乙酰基酶1 組蛋白乙酰化組蛋白甲基化

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目的明確哮喘大鼠肺T淋巴細胞中的組蛋白去乙酰基酶1( HDAC1) 蛋白表達水平及組蛋白整體乙酰化和甲基化水平, 探討其在哮喘發病機制中的作用。方法 16 只Wistar 大鼠隨機分為對照組和哮喘組( 每組8 只) , 用卵白蛋白( OVA) 致敏并激發建立哮喘大鼠模型。通過哮喘臨床表現、氣道高反應性測定、肺組織HE 染色、血清和BALF中細胞因子IL-4、γ干擾素( IFN-γ) 及IgEELISA 測定, 判斷哮喘大鼠模型是否成功。分離肺T 細胞并進行純度鑒定。Western blot 檢測肺T細胞HDAC1 蛋白表達水平, 組蛋白H3、H4 整體乙酰化, 以及H3k9 整體二甲基化水平。結果與對照組比較, 哮喘組HDAC1 蛋白表達水平低于對照組( P lt; 0. 05) , 組蛋白H3、H4 整體乙酰化水平和H3k9 整體二甲基化水平差異均無統計學意義。結論肺T 細胞HDAC1 可能參與了支氣管哮喘的發病環節, 組蛋白整體乙酰化和甲基化水平與哮喘發病無明顯相關性, HDAC1 對組蛋白修飾作用可能是一個基因轉錄特異性事件。

引用本文： 李成業,郭雪君,甘麗杏,丁濤,顧問. 哮喘大鼠肺T 細胞中組蛋白去乙酰基酶1 的表達及對組蛋白修飾的影響. 中國呼吸與危重監護雜志, 2010, 9(3): 259-263. doi: 復制

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14.	Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 .
15.	Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 .
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17.	Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120.

1. Kaminuma O, Kitamura F, Miyatake S, et al. T-box 21 transcription factor is responsible for distorted T( H) 2 differentiation in human peripheral CD4 + T cells. J Allergy Clin Immunol,2009, 123: 813-23.
2. Su RC, Becker AB, Kozyrskyj AL, et al. Epigenetic regulation of established human type 1 versus type 2 cytokine responses. JAllergyClin Immunol, 2008, 121: 57-63.
3. 李成業, 甘麗杏, 郭雪君. 支氣管哮喘的表觀遺傳學. 中華結核和呼吸雜志, 2009, 32 : 759-761.
4. Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med, 2002, 166 : 392-396.
5. Miller RL, Ho SM. Environmental Epigenetics and Asthma. Am J Respir Crit Care Med, 2008 , 177: 567-573 .
6. El-Biaze M, Boniface S, Koscher V, et al. T cell activation, from atopy to asthma: more a paradox. Allergy, 2003 , 58: 844-853.
7. Marmorstein R. Protein modules that manipulate histone tails for chromatin regulation. Nat Rev Mol Cell Biol, 2001, 2: 422-432.
8. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121 :580-584.
9. Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanismof transcriptional regulation. Annu Rev Biochem, 1998 ,67: 545-579 .
10. Peterson S, Jackson V. Acetylation of H4 suppresses the repressive effects of the N-termini of histones H3 /H4 and facilitates the formation of positively coiled DNA. Biochemistry, 2008 , 47: 7053 -7065.
11. Ito K, Charron CE, Adcock IM. Impact of protein acetylation in inflammatory lung diseases. Pharmacol Ther, 2007, 116 : 249-265.
12. Bannister AJ, Kouzarides T. Reversing histone methylation. Nature,2005, 436: 1103-1106.
13. Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett, 2009, 280 : 168-176.
14. Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 .
15. Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 .
16. Choi JH, Oh SW, Kang MS, et al. Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy, 2005, 35 :89-96.
17. Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120.

《中國呼吸與危重監護雜志》

哮喘大鼠肺T 細胞中組蛋白去乙酰基酶1 的表達及對組蛋白修飾的影響

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《中國呼吸與危重監護雜志》

哮喘大鼠肺T 細胞中組蛋白去乙酰基酶1 的表達及對組蛋白修飾的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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Content

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