ROS/Src /JNK 信號通路在香煙誘導氣道上皮細胞黏液高分泌中的作用_《中國呼吸與危重監護雜志》

作者：

田川 ¹ , 李琪 ² ,  周向東 ²

1 南川市人民醫院呼吸內科（重慶南川 400582）;;
2 重慶醫科大學附屬第二醫院呼吸內科（重慶 400010）;

關鍵詞：

黏蛋白香煙活性氧 Src JNK

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目的探討在香煙誘導氣道上皮細胞黏蛋白MUC5AC 表達過程中Src / JNK 信號通路的作用。方法香煙抽提物預處理的人氣道上皮A549 細胞, 分別以活性氧( ROS) 清除劑DMTU、JNK 特異性抑制劑SP600125 及Src 激酶抑制劑PP2 干預。測定各組細胞中ROS 的含量, 采用RT-PCR、ELISA 法觀察細胞黏蛋白( MUC) 5AC轉錄水平及培養上清液中MUC5AC 蛋白水平的改變,以Western blot 法檢測細胞表皮生長因子受體( EGFR) 的蛋白表達。結果細胞暴露于不同濃度的香煙抽提物中, ROS的量呈濃度遞增; ROS清除劑DMTU 顯著降低香煙所致的Src 磷酸化; Src 特異性抑制劑PP2 處理組中的JNK 磷酸化水平與對照組比較有明顯下降, MUC5AC 的表達水平也明顯降低; JNK特異性抑制劑SP600125 組中MUC5AC 的蛋白表達和基因轉錄水平較對照組均明顯降低。結論 ROS-Src-JNK信號通路可能參與A549 上皮細胞中MUC5AC 的表達調控。

引用本文： 田川,李琪,周向東. ROS/Src /JNK 信號通路在香煙誘導氣道上皮細胞黏液高分泌中的作用. 中國呼吸與危重監護雜志, 2009, 09(2): 127-130. doi: 復制

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2.	Psarras S, Caramori G, Contoli M, et al. Oxidants in asthma and in chronic obstructive pulmonary disease( COPD) . Curr Pharm Des,2005, 11: 2053-2062.
3.	Shao MX, Nakanaga T, Nadel JA. Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial( NCI-H292 ) cells. Am J Physiol Lung Cell Mol Physiol, 2004, 287: L420-L427.
4.	Takeyama K, Jung B, Shim JJ, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol, 2001, 280:L165-L172.
5.	周向東, 童瑾, 蘭箭. 慢性阻塞性肺疾病患者氣道黏蛋白分子表型的研究. 中華結核和呼吸雜志, 2002, 25: 437.
6.	YoshizumM, Abe JI, Haendeler J, et al. Src and Cas Mediate JNK Activation but Not ERK1 /2 and p38 Kinases by Reactive Oxygen Species. J Biol Chem, 2000, 275: 11706-11712.
7.	Nakamura Y, Romberger DJ, Tate L, et al. Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis. Am J Respir Crit Care Med, 1995, 151: 1497-1503.
8.	Ma C, Bower KA, Lin H, et al. The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivaion. Biochem Pharmacol, 2005, 69 : 1785 -1794 .
9.	Pinkus R, Weiner LM, Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-κB, and gutathione-s transferase gene expression. J Biol Chem, 1996, 271: 13422-13429.
10.	Chen K, Vita JA, Berk BC, et al. c-Jun N-terminal Kinase Activation.
11.	Meurer S, Pioch S, Gross S. Reactive Oxygen Species Induce Tyrosine Phosphorylation of and Src Kinase Recruitment to NOsensitive Guanylyl Cyclase. J Biol Chen, 2005, 280: 33149-33156.
12.	Li JD, Feng W, Gallup M. et al. Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci USA, 1998, 95: 5718-5723.

1. by Hydrogen Peroxide in Endothelial Cells Involves Src-dependent Epidermal Growth Factor Receptor Transactivation. J Biol Chem,2001, 276: 16045-16050.
2. Psarras S, Caramori G, Contoli M, et al. Oxidants in asthma and in chronic obstructive pulmonary disease( COPD) . Curr Pharm Des,2005, 11: 2053-2062.
3. Shao MX, Nakanaga T, Nadel JA. Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial( NCI-H292 ) cells. Am J Physiol Lung Cell Mol Physiol, 2004, 287: L420-L427.
4. Takeyama K, Jung B, Shim JJ, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol, 2001, 280:L165-L172.
5. 周向東, 童瑾, 蘭箭. 慢性阻塞性肺疾病患者氣道黏蛋白分子表型的研究. 中華結核和呼吸雜志, 2002, 25: 437.
6. YoshizumM, Abe JI, Haendeler J, et al. Src and Cas Mediate JNK Activation but Not ERK1 /2 and p38 Kinases by Reactive Oxygen Species. J Biol Chem, 2000, 275: 11706-11712.
7. Nakamura Y, Romberger DJ, Tate L, et al. Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis. Am J Respir Crit Care Med, 1995, 151: 1497-1503.
8. Ma C, Bower KA, Lin H, et al. The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivaion. Biochem Pharmacol, 2005, 69 : 1785 -1794 .
9. Pinkus R, Weiner LM, Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-κB, and gutathione-s transferase gene expression. J Biol Chem, 1996, 271: 13422-13429.
10. Chen K, Vita JA, Berk BC, et al. c-Jun N-terminal Kinase Activation.
11. Meurer S, Pioch S, Gross S. Reactive Oxygen Species Induce Tyrosine Phosphorylation of and Src Kinase Recruitment to NOsensitive Guanylyl Cyclase. J Biol Chen, 2005, 280: 33149-33156.
12. Li JD, Feng W, Gallup M. et al. Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci USA, 1998, 95: 5718-5723.

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《中國呼吸與危重監護雜志》

ROS/Src /JNK 信號通路在香煙誘導氣道上皮細胞黏液高分泌中的作用

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《中國呼吸與危重監護雜志》

ROS/Src /JNK 信號通路在香煙誘導氣道上皮細胞黏液高分泌中的作用

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