Tobacco carcinogen NNK transporter MRP2 regulates CFTR function in lung epithelia: implications for lung cancer.
Tobacco carcinogen NNK transporter MRP2 regulates CFTR function in lung epithelia: implications for lung cancer.
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DOI：
10.1016/j.canlet.2009.12.009
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发表时间：
2010-06-28
期刊：
影响因子：
9.7
通讯作者：
Naren, Anjaparavanda P.
中科院分区：
文献类型：
--
作者：
Li, Chunying;Schuetz, John D.;Naren, Anjaparavanda P.
肺癌是美国癌症死亡的主要原因。约85%的肺癌与烟草烟雾有关，其中50多种致癌物质已被确认，其中最丰富的是4-(甲基亚硝基)-1-(3-吡啶)-1-丁酮(NNK)。人肺上皮细胞是抵御烟草特有致癌物的第一道防线，其中位于呼吸道顶端的受体、转运体和离子通道可能在这种天然的烟草烟雾防御中起着关键作用。在此，我们发现多药耐药蛋白-2(MRP2)和囊性纤维化跨膜传导调节蛋白(CFTR)这两种三磷酸腺苷结合盒(ABC)转运蛋白定位于极化肺上皮细胞质膜的顶面。我们观察到CFTR和MRP2之间存在功能偶联，这种偶联可能是由PDZ蛋白介导的。我们还观察到包含CFTR、MRP2和PDZ蛋白的大分子复合体的存在，这可能构成这两个ABC转运蛋白之间调控合作的基础。我们的研究结果对与吸烟相关的肺部疾病(如与吸烟相关的肺气肿、慢性阻塞性肺疾病和肺癌)具有重要意义。
Lung cancer is the leading cause of cancer death in the United States. About 85% of all lung cancers are linked to tobacco smoke, in which more than 50 lung carcinogens have been identified and one of the most abundant is 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone (NNK). The human lung epithelium constitutes the first line of defense against tobacco specific carcinogens, in which apically-localized receptors, transporters, and ion channels in the airway may play a critical role in this native defense against tobacco smoke. Here we showed that multidrug resistance protein-2 (MRP2) and cystic fibrosis transmembrane conductance regulator (CFTR), two ATP-binding cassette (ABC) transporters, are localized to the apical surfaces of plasma membrane in polarized lung epithelial cells. We observed that there is a functional coupling between CFTR and MRP2 that may be mediated by PDZ proteins. We also observed the existence of a macromolecular complex containing CFTR, MRP2, and PDZ proteins, which might form the basis for the regulatory cooperation between these two ABC transporters. Our results have important implications for cigarette smoke-associated lung diseases (such as smoke-related emphysema, chronic obstructive pulmonary disease, and lung cancer).
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DOI：
10.1016/s0006-291x(03)00196-7
发表时间：
2003-03-14
影响因子：
3.1
作者：
Hegedüs, T;Sessler, T;Sarkadi, B
通讯作者：
Sarkadi, B
影响因子：
4.6
作者：
Proulx, LI;Gaudreault, M;Bissonnette, ÉY
通讯作者：
Bissonnette, ÉY
DOI：
10.1164/rccm.200508-1330oc
发表时间：
2006-05-15
影响因子：
24.7
作者：
Cantin, Andre M.;Hanrahan, John W.;Durie, Peter
通讯作者：
Durie, Peter
DOI：
10.1073/pnas.0135434100
发表时间：
2003-01-07
影响因子：
11.1
作者：
Naren, AP;Cobb, B;Clancy, JP
通讯作者：
Clancy, JP
DOI：
10.1084/jem.20050421
发表时间：
2005-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li C;Dandridge KS;Di A;Marrs KL;Harris EL;Roy K;Jackson JS;Makarova NV;Fujiwara Y;Farrar PL;Nelson DJ;Tigyi GJ;Naren AP
通讯作者：
Naren AP