目的 探討在香煙誘導(dǎo)氣道上皮細(xì)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(yù)處理的人氣道上皮A549 細(xì)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(yù)。測定各組細(xì)胞中ROS 的含量, 采用RT-PCR、ELISA 法觀察細(xì)胞黏蛋白( MUC) 5AC轉(zhuǎn)錄水平及培養(yǎng)上清液中MUC5AC 蛋白水平的改變,以Western blot 法檢測細(xì)胞表皮生長因子受體( EGFR) 的蛋白表達。結(jié)果 細(xì)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(zhuǎn)錄水平較對照組均明顯降低。結(jié)論 ROS-Src-JNK信號通路可能參與A549 上皮細(xì)胞中MUC5AC 的表達調(diào)控。
引用本文： 田川,李琪,周向東. ROS/Src /JNK 信號通路在香煙誘導(dǎo)氣道上皮細(xì)胞黏液高分泌中的作用. 中國呼吸與危重監(jiān)護雜志, 2009, 09(2): 127-130. doi: 復(fù)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(jié)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(jié)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.