Peroxynitrite and the regulation of Na+,K+-ATPase activity by angiotensin II in the rat proximal tubule
Peroxynitrite and the regulation of Na+,K+-ATPase activity by angiotensin II in the rat proximal tubule
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DOI：
10.1016/s1089-8603(02)00003-4
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发表时间：
2002-08-01
影响因子：
3.9
通讯作者：
Mayeux, PR
中科院分区：
文献类型：
--
作者：
Zhang, CJ;Imam, SZ;Mayeux, PR
NO与超氧化物自发反应产生强氧化剂过氧亚硝酸盐。研究旨在研究一氧化氮衍生氧化剂和过氧亚硝酸盐对新分离的大鼠近端小管血管紧张素11 （ANG II）对Na+，K+- atp酶活性的调节作用。在皮摩尔浓度下，ANG 11刺激Na+，K+- atp酶活性，但在纳摩尔浓度下，刺激消失。用超氧化物歧化酶（SOD）检测超氧化物的作用，用去铁胺（DFO）和尿酸（UA）检测过氧亚硝酸盐的作用。超氧化物歧化酶（SOD） （200 U/mL，预孵育5 min）与单独10(-7)M相比可恢复ANG 11的刺激作用（1.31 +/- 0.08倍；n = 4; P < 0.05），提示其与超氧化物有关。DFO（100妈，预孵育5分钟）也恢复了ang11的刺激作用（1.40 +/- 0.08倍，n = 4, P < 0.05，与单独10(-7)M相比），UA（1.22 +/- 0.07倍，n = 5, P < 0.05，与单独10(-7)M相比）。NO合成抑制剂n -单甲基- l-精氨酸（L-NMMA, 2 mM；预孵育5分钟）也揭示了10(-7)M时ANG 11的刺激作用（与单独10(-7)M相比，为1.4 +/- 0.1倍；n = 7; P < 0.05）。3-硝基酪氨酸（3-NT）的生成进一步证明了过氧亚硝酸盐的生成。对照（0.0054 +/- 0.0019 3-NT/100酪氨酸）和对照（0.019 +/- 0.0058 3-NT/100酪氨酸，P < 0.05, n = 4）处理的小管3-NT增加了3.5倍，L-NMMA阻止了3-NT的增加。这些数据提示过氧亚硝酸盐信号参与了肾脏Na+，K+- atp酶活性的调节。(C) 2002 Elsevier Science （USA）。版权所有。
NO reacts spontaneously with superoxide to produce the potent oxidant peroxynitrite. Studies were designed to examine the role of NO-derived oxidants and peroxynitrite on the regulation of Na+,K+-ATPase activity by angiotensin 11 (ANG II) freshly isolated rat proximal tubules. At picomolar concentrations ANG 11 stimulates Na+,K+-ATPase activity, but at nanomolar concentrations stimulation is lost. Superoxide dismutase (SOD) was used to examine the role of superoxide and deferoxamine (DFO) and uric acid (UA) were used to examine the role of peroxynitrite. SOD (200 U/mL, 5-min preincubation) restored the stimulatory effect of ANG 11 (1.31 +/- 0.08-fold; n = 4; P < 0.05 compared to 10(-7) M alone), suggesting a role for superoxide. DFO (100 mum, 5-min preincubation) also restored the stimulatory effect of ANG 11 (1.40 +/- 0.08-fold; n = 4; P < 0.05, compared to 10(-7) M alone), as did UA (1.22 +/- 0.07-fold; n = 5; P < 0.05, compared to 10(-7) M alone). The NO synthesis inhibitor, N-monomethyl-L-arginine (L-NMMA, 2 mM; 5-min preincubation), also unmasked a stimulatory effect of ANG 11 at 10(-7) M (1.4 +/- 0.1-fold; n = 7; P < 0.05, compared to 10(-7) M alone). The generation of peroxynitrite was further evidenced by the formation of 3-nitrotyrosine (3-NT). 3-NT increased 3.5-fold in tubules exposed to ANG 11 (10(-7) M) (0.0054 +/- 0.0019 3-NT/100 tyrosines for control and 0.019 +/- 0.0058 3-NT/100 tyrosines for ANG 11, P < 0.05; n = 4) and L-NMMA prevented the increase. These data suggest that peroxynitrite signaling participates in the regulation of renal of Na+,K+-ATPase activity. (C) 2002 Elsevier Science (USA). All rights reserved.