The nitric oxide system response to hypoxia/reoxygenation in the aged cerebral cortex

The nitric oxide system response to hypoxia/reoxygenation in the aged cerebral cortex
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DOI:
10.1016/j.exger.2007.09.006
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发表时间:
2007-12-01
影响因子:
3.9
通讯作者:
Martinez-Lara, E.
Martinez-Lara, E.
中科院分区:
医学2区
文献类型:
--
作者:
Canuelo, A.;Siles, E.;Martinez-Lara, E.

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老年人更容易受到缺氧损伤,但对衰老大脑中一氧化氮(NO)系统对缺氧的反应知之甚少。分析了增龄对低压缺氧/复氧大鼠大脑皮层一氧化氮合酶(NOS)表达和活性的影响。在老年动物中,NOx和活性没有显著变化表明在这种病理情况下涉及NO产生的系统的反应较弱。缺氧后两个年龄组的nNOS蛋白水平保持不变和相似,虽然在老年动物的mRNA没有变化,始终低于成年人。缺氧后即刻eNOS mRNA和蛋白表达均增加。然而,尽管两个年龄组的eNOS蛋白水平非常相似,但老年动物的增加出现得较晚,并且持续性较差。实时定量RT-PCR显示了类似的基础诱导型一氧化氮合酶(iNOS)mRNA的表达,在复氧反应晚,主要是在老年大鼠。然而,在任何年龄组中均未检测到iNOS蛋白或活性。总之,我们的研究结果表明,衰老减弱了一氧化氮系统的反应,缺氧损伤,特别是在eNOS水平,其活性是至关重要的维持血管稳态。(c)2007爱思唯尔公司All rights reserved.
Aged individuals are more susceptible to hypoxic insults, but little is known about the response of the nitric oxide (NO) system to hypoxia in the senescent brain. We have analysed the effect of aging on the hypobaric hypoxia/reoxygenation NO synthase (NOS) expression and activity in the cerebral cortex. In aged animals, the absence of significant changes in NOx and activity indicates a weaker response of the systems involving NO production in this pathological situation. The nNOS protein levels remained invariable and similar in both age groups after hypoxia, although in aged animals the mRNA did not change and was consistently lower than in adults. Both eNOS mRNA and protein increased shortly after hypoxia. However, although eNOS protein levels were quite similar in both age groups, the increase appeared later and was less persistent in aged animals. Real-time RT-PCR revealed a similar basal inducible NOS (iNOS) mRNA expression that responded late in reoxygenation, mainly in aged rats. However, neither iNOS protein nor activity was detected in any age group. Altogether our results indicate that aging attenuates the response of the NO system to a hypoxic injury, particularly at eNOS level, the activity of which is crucial for maintaining vascular homeostasis. (c) 2007 Elsevier Inc. All rights reserved.