Aldosterone stimulates superoxide production in macula densa cells.
Aldosterone stimulates superoxide production in macula densa cells.
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醛固酮刺激致密斑细胞中超氧化物的产生。
DOI：
10.1152/ajprenal.00596.2010
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Liu,Ruisheng
中科院分区：
文献类型：
--
作者：
Zhu,Xiaolong;ManningJr,RDavis;Lu,Deyin;Gomez-Sanchez,CelsoE;Fu,Yiling;Juncos,LuisA;Liu,Ruisheng
调节小管肾小球反馈（TGF）介导的传入小动脉收缩的两个主要因素是致密斑（MD）细胞释放超氧化物（O2−）和一氧化氮（NO）。MD O2−使NO失活;然而，在增加MD O2−释放的因素中，醛固酮的作用尚不清楚。我们假设醛固酮激活MD细胞上的盐皮质激素受体（MR），导致由于环氧化酶-1（考克斯-2）和NOX-2和NOX-4（NAD（P）H氧化酶的同种型）的上调而导致O2−产生增加。对具有MD细胞特性的肾上皮细胞系MMDD 1细胞进行研究。RT-PCR和Western blotting证实了MR的表达。醛固酮（10− 8 mol/l，30分钟）使MMDD 1细胞的O2−产量增加一倍，而这一点完全被10− 5 mol/l依普利酮的MR抑制所阻断。RT-PCR、实时PCR和蛋白质印迹证实醛固酮诱导的考克斯-2、NOX-2和NOX-4表达增加。抑制考克斯-2（NS 398）、NADPH氧化酶（夹竹桃黄素）或两者的组合，也能在相同程度上阻断醛固酮诱导的O2−生成。这些数据表明，醛固酮刺激的MD O2−产生由考克斯-2和NADPH氧化酶介导。接下来，考克斯-2小干扰RNA（siRNA）特异性降低考克斯-2 mRNA，而不影响NOX-2或NOX-4 mRNA。在存在考克斯-2 siRNA的情况下，醛固酮诱导的考克斯-2、NOX-2和NOX-4 mRNA的增加以及O2−的产生被完全阻断，这表明考克斯-2导致NOX-2和NOX-4的表达增加。结论：1）MD细胞表达MR;2）醛固酮通过激活MR增加O2−的产生; 3）醛固酮刺激考克斯-2，COX-2进一步激活NOX-2和NOX-4并产生O2−。MD中O2−和NO之间的平衡对于调节TGF非常重要。
Two major factors which regulate tubuloglomerular feedback (TGF)-mediated constriction of the afferent arteriole are release of superoxide (O2−) and nitric oxide (NO) by macula densa (MD) cells. MD O2−inactivates NO; however, among the factors that increase MD O2−release, the role of aldosterone is unclear. We hypothesize that aldosterone activates the mineralocorticoid receptor (MR) on MD cells, resulting in increased O2−production due to upregulation of cyclooxygenase-1 (COX-2) and NOX-2, and NOX-4, isoforms of NAD(P)H oxidase. Studies were performed on MMDD1 cells, a renal epithelial cell line with properties of MD cells. RT-PCR and Western blotting confirmed the expression of MR. Aldosterone (10−8mol/l for 30 min) doubled MMDD1 cell O2−production, and this was completely blocked by MR inhibition with 10−5mol/l eplerenone. RT-PCR, real-time PCR, and Western blotting demonstrated aldosterone-induced increases in COX-2, NOX-2, and NOX-4 expression. Inhibition of COX-2 (NS398), NADPH oxidase (apocynin), or a combination blocked aldosterone-induced O2−production to the same degree. These data suggest that aldosterone-stimulated MD O2−production is mediated by COX-2 and NADPH oxidase. Next, COX-2 small-interfering RNA (siRNA) specifically decreased COX-2 mRNA without affecting NOX-2 or NOX-4 mRNAs. In the presence of the COX-2 siRNA, the aldosterone-induced increases in COX-2, NOX-2, and NOX-4 mRNAs and O2−production were completely blocked, suggesting that COX-2 causes increased expression of NOX-2 and NOX-4. In conclusion1) MD cells express MR;2) aldosterone increases O2−production by activating MR; and3) aldosterone stimulates COX-2, which further activates NOX-2 and NOX-4 and generates O2−. The resulting balance between O2−and NO in the MD is important in modulating TGF.
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醛固酮及其酸不稳定结合物的肾小管处理。
影响因子：
15.9
作者：
M. Scurry;L. Shear;K. Barry
通讯作者：
K. Barry
DOI：
10.1152/ajpheart.00953.2007
发表时间：
2008-06-01
影响因子：
4.8
作者：
DeMarco, Vincent G.;Habibi, Javad;Dellsperger, Kevin C.
通讯作者：
Dellsperger, Kevin C.
影响因子：
19.6
作者：
Hollenberg, NK;Stevanovic, R;Fisher, NDL
通讯作者：
Fisher, NDL
DOI：
10.1152/ajpregu.00762.2009
发表时间：
2010-03-01
影响因子：
2.8
作者：
Fu, Yiling;Zhang, Rui;Liu, Ruisheng
通讯作者：
Liu, Ruisheng
DOI：
10.1152/ajprenal.90204.2008
发表时间：
2008-09
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Ruisheng Liu;O. Carretero;Yilin Ren;Hong Wang;J. Garvin
通讯作者：
Ruisheng Liu;O. Carretero;Yilin Ren;Hong Wang;J. Garvin