Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear factor of activated T cells.
Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear factor of activated T cells.
复制标题
DOI：
10.1159/000333066
复制
发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Gonzalez Bosc LV
中科院分区：
文献类型：
--
作者：
Albertoni Borghese MF;Bettini LM;Nitta CH;de Frutos S;Majowicz M;Gonzalez Bosc LV
我们以前已经表明，水通道蛋白-2（AQP 2）在慢性抑制一氧化氮合酶造成高血压的大鼠肾髓质中下调。研究表明，AQP 2的表达受活化T细胞的钙调神经磷酸酶/核因子（NFATc）的调节。一氧化氮（NO）通过c-Jun-N-末端激酶2（JNK 2）调节NFATc的活性。因此，我们假设NO的增加增强了NFATc介导的AQP 2启动子活性的上调。AQP 2 mRNA和蛋白在小鼠肾乳头中均有表达。使用AQP 2启动子荧光素酶报告基因转染的MDCK细胞和NFAT荧光素酶报告基因转染的MDCK细胞分别测定AQP 2启动子活性和NFATc活性。将细胞与NFATc和NO途径的经典激活剂和抑制剂一起孵育。我们的研究结果表明，Ca 2+和NO具有协同作用，导致增加AQP 2 mRNA和蛋白在小鼠乳头和激活的AQP 2启动子在肾细胞。此外，NO增强Ca 2+诱导的NFATc活化。潜在的机制涉及通过蛋白激酶G介导的JNK 1/2抑制增加NFATc核输入和减少输出。这是第一项定义NO和NFATc在控制AQP 2（一种重要的肾脏蛋白）中的新调节作用的研究。
We have previously shown that aquaporin-2 (AQP2) is down-regulated in the renal medulla of rats made hypertensive by chronic inhibition of nitric oxide synthase. It has been shown that AQP2 expression is regulated by the calcineurin/nuclear factor of activated T cells (NFATc). Nitric oxide (NO) regulates the activity of NFATc via c-Jun-N-terminal kinase 2 (JNK2). Therefore, we hypothesized that increases in NO enhance NFATc-mediated up-regulation of AQP2 promoter activity. AQP2 mRNA and protein expression were detected in mouse renal papilla. AQP2 promoter luciferase reporter- and NFAT luciferase reporter-transfected MDCK cells were used to determine AQP2 promoter activity and NFATc activity, respectively. Cells were incubated with classic activators and inhibitors of NFATc and the NO pathway. Our results demonstrate that both Ca2+ and NO have a synergistic effect resulting in an increase in AQP2 mRNA and protein in mouse papilla and activation of the AQP2 promoter in kidney-derived cells. In addition, NO enhances Ca2+-induced NFATc activation. The underlying mechanism involves increased NFATc nuclear import and decreased export via protein kinase G-mediated inhibition of JNK1/2. This is the first study defining novel regulatory roles for NO and NFATc in the control of AQP2, which is an important renal protein.
登录
查看更多内容
影响因子：
--
作者：
Borghese, Maria F. Albertoni;Majowicz, Monica P.;Vidal, Norberto A.
通讯作者：
Vidal, Norberto A.
影响因子：
20.1
作者：
Lima B;Forrester MT;Hess DT;Stamler JS
通讯作者：
Stamler JS
影响因子：
6.1
作者：
Kasono, K;Saito, T;Ishikawa, SE
通讯作者：
Ishikawa, SE
影响因子：
20.1
作者：
MacDonnell SM;Weisser-Thomas J;Kubo H;Hanscome M;Liu Q;Jaleel N;Berretta R;Chen X;Brown JH;Sabri AK;Molkentin JD;Houser SR
通讯作者：
Houser SR
DOI：
10.1073/pnas.96.13.7214
发表时间：
1999-06-22
影响因子：
11.1
作者：
López-Rodríguez, C;Aramburu, J;Rao, A
通讯作者：
Rao, A