Inhaled nitric oxide prevents 3-nitrotyrosine formation in the lungs of neonatal mice exposed to >95% oxygen.
Inhaled nitric oxide prevents 3-nitrotyrosine formation in the lungs of neonatal mice exposed to >95% oxygen.
复制标题
吸入一氧化氮可防止在暴露于95％氧气的新生小鼠的肺中形成3-硝基酪氨酸。
DOI：
10.1007/s00408-010-9235-6
复制
发表时间：
2010-06
期刊：
影响因子：
5
通讯作者：
Nelin LD
中科院分区：
文献类型：
--
作者：
Stenger MR;Rose MJ;Joshi MS;Rogers LK;Chicoine LG;Bauer JA;Nelin LD
吸入一氧化氮正被评估为对有支气管肺发育不良(BPD)风险的患者的预防性治疗。在超氧化物存在下，一氧化氮(NO)生成过氧亚硝酸盐，过氧亚硝酸盐与蛋白质上的酪氨酸残基反应生成3-硝基酪氨酸(3-NT)。然而，一氧化氮也可以作为抗氧化剂，最近被发现可以改善早产儿的氧化平衡。因此，我们测试了这样的假设，即在高氧暴露中添加治疗相关浓度(10ppm)的NO将导致肺中3-NT的形成减少。FVB小鼠幼鼠出生后24小时内暴露于室内空气(21%O2)或95%O2(含或不含10ppm NO)中。在第一组研究中，体重和存活时间被监测了7天，暴露在95%O2中会导致体重增加受阻，7天后死亡率接近100%。然而，暴露在>；95%O2+NO中的幼鼠比单独暴露在>；95%O2中的幼鼠死亡更早。在第二组研究中，72小时后取肺。免疫组织化学显示，NO的加入降低了暴露在室内空气和高氧环境中的幼鼠的肺泡、支气管和血管3-NT染色。暴露在95%氧气+NO中的动物的肺亚硝酸盐水平高于单独暴露在95%氧气中的动物。暴露72小时后，检测髓过氧化物酶、单核细胞趋化蛋白-1和细胞间黏附分子-1的蛋白水平，发现暴露于95%O2的幼鼠肺中髓过氧化物酶、单核细胞趋化蛋白-1和细胞间黏附分子-1的蛋白水平最高。这种高氧诱导的蛋白表达可被10ppm的NO显著减弱。我们认为，在>；95%O2存在的情况下，过氧亚硝酸盐的形成导致蛋白质硝化；然而，在>；95%O2暴露中添加过量的NO通过NO与过氧亚硝酸盐反应生成亚硝酸盐和NO2来阻止3-NT的形成。我们推测，随着NO的加入，蛋白质硝化减少可能是限制高氧性肺损伤的一个潜在机制。
Inhaled nitric oxide is being evaluated as a preventative therapy for patients at risk for bronchopulmonary dysplasia (BPD). Nitric oxide (NO), in the presence of superoxide, forms peroxynitrite, which reacts with tyrosine residues on proteins to form 3-nitrotyrosine (3-NT). However, NO can also act as an antioxidant and was recently found to improve the oxidative balance in preterm infants. Thus, we tested the hypothesis that the addition of a therapeutically relevant concentration (10 ppm) of NO to a hyperoxic exposure would lead to decreased 3-NT formation in the lung. FVB mouse pups were exposed to either room air (21% O2) or >95% O2 with or without 10 ppm NO within 24 h of birth. In the first set of studies, body weights and survival were monitored for 7 days, and exposure to >95% O2 resulted in impaired weight gain and near 100% mortality by 7 days. However, the mortality occurred earlier in pups exposed to >95% O2 + NO than in pups exposed to >95% O2 alone. In a second set of studies, lungs were harvested at 72 h. Immunohistochemistry of the lungs at 72 h revealed that the addition of NO decreased alveolar, bronchial, and vascular 3-NT staining in pups exposed to both room air and hyperoxia. The lung nitrite levels were higher in animals exposed to >95% oxygen + NO than in animals exposed to >95% oxygen alone. The protein levels of myeloperoxidase, monocyte chemotactic protein-1, and intracellular adhesion molecule-1 were assessed after 72 h of exposure and found to be greatest in the lungs of pups exposed to >95% O2. This hyperoxia-induced protein expression was significantly attenuated by the addition of 10 ppm NO. We propose that in the presence of >95% O2, peroxynitrite formation results in protein nitration; however, adding excess NO to the >95% O2 exposure prevents 3-NT formation by NO reacting with peroxynitrite to produce nitrite and NO2. We speculate that the decreased protein nitration observed with the addition of NO may be a potential mechanism limiting hyperoxic lung injury.
登录
查看更多内容
DOI：
10.1152/ajplung.1999.277.3.l596
发表时间：
1999-09-01
影响因子：
4.9
作者：
Howlett, CE;Hutchison, JS;Fliss, H
通讯作者：
Fliss, H
影响因子：
158.5
作者：
Ballard, Roberta A.;Truog, William E.;Coburn, Christine E.
通讯作者：
Coburn, Christine E.
影响因子：
3.6
作者：
Kinsella, JP;Parker, TA;Abman, SH
通讯作者：
Abman, SH
DOI：
10.1136/fn.86.1.f41
发表时间：
2002-01-01
影响因子：
4.4
作者：
Clark, PL;Ekekezie, II;Truog, WE
通讯作者：
Truog, WE
DOI：
10.1165/ajrcmb.24.4.4218
发表时间：
2001-04-01
影响因子：
6.4
作者：
Kobayashi, H;Hataishi, R;Jones, RC
通讯作者：
Jones, RC