Chronic myocardial hypoxia increases nitric oxide synthase and decreases caveolin-3
Chronic myocardial hypoxia increases nitric oxide synthase and decreases caveolin-3
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DOI：
10.1016/s0891-5849(00)00364-6
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发表时间：
2000-10-15
影响因子：
7.4
通讯作者：
Baker, JE
中科院分区：
文献类型：
--
作者：
Shi, Y;Pritchard, KA;Baker, JE
一氧化氮合酶（NOS）在心肌缺血保护中起重要作用。出生后的慢性缺氧会增加心肌中的NOS活性，从而增强一氧化氮的产生和对缺血的抵抗力。我们研究了慢性缺氧对NOS基因和蛋白表达的影响，以及NOS蛋白与caveolin-3的关联。兔出生后在常氧（F1O2 = 0.21）和缺氧（F1O2 = 0.12）环境下饲养9 d，然后分离心脏。核糖核酸酶保护实验显示，慢性缺氧不改变NOS1、NOS2或NOS3的NOS转录水平。最丰富的转录本是NOS3。Western分析显示NOS3是唯一检测到的异构体。NOS3免疫沉淀物免疫印迹显示，慢性缺氧使NOS3蛋白增加2.0 +/- 0.1倍，使能与NOS3共沉淀的小窝蛋白-3减少5.5 +/- 0.9倍。常氧和低氧心脏的免疫印迹显示，慢性缺氧使心脏匀浆中小窝蛋白-3的含量降低了2.2 +/- 0.5倍。这些数据表明，在慢性缺氧增加心肌NOS3活性的机制中，小窝蛋白-3的减少发挥了作用。(C) 2000 Elsevier Science Inc.；
Nitric oxide synthase (NOS) is believed to play an important role in protecting the myocardium against ischemia. Chronic hypoxia from birth increases NOS activity in the myocardium resulting in enhanced nitric oxide production and increased resistance to ischemia. We examined the effects of chronic hypoxia on NOS gene and protein expression and on NOS protein association with caveolin-3. Rabbits were raised from birth in a normoxic (F1O2 = 0.21) or a hypoxic (F1O2 = 0.12) environment for 9 d, and then the hearts were isolated. Ribonuclease protection assays revealed that chronic hypoxia did not alter NOS transcript levels for NOS1, NOS2, or NOS3. The most abundant transcript was NOS3. Western analysis revealed NOS3 was the only isoform detected. Immunoblots of NOS3 immunoprecipitates showed that chronic hypoxia increases NOS3 protein by 2.0 +/- 0.1 -fold and decreases the amount of caveolin-3 that can be coprecipitated with NOS3 by 5.5 +/- 0.9-fold. Immunoblots of normoxic and hypoxic hearts showed that chronic hypoxia decreases the amount of caveolin-3 in heart homogenates by 2.2 +/- 0.5-fold. These data suggest that a decrease in caveolin-3 plays a role in the mechanisms by which chronic hypoxia increases NOS3 activity in the myocardium. (C) 2000 Elsevier Science Inc.