The effect of age on cyclooxygenase-2 gene expression:: NF-κb activation and IκBα degradation
The effect of age on cyclooxygenase-2 gene expression:: NF-κb activation and IκBα degradation
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DOI：
10.1016/s0891-5849(99)00274-9
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发表时间：
2000-03-01
影响因子：
7.4
通讯作者：
Chung, HY
中科院分区：
文献类型：
--
作者：
Kim, HJ;Kim, KW;Chung, HY
氧化应激增加导致核因子-kappaB的激活，被认为在环氧合酶-2(COX-2)的表达中起着关键作用，COX-2是前炎性前列腺素合成的关键酶。在目前的研究中，我们研究了衰老过程是否影响大鼠肾脏氧化还原敏感型核因子-kappaB的状态，以及这种与年龄相关的调节与COX-2基因表达和COX衍生的活性氧(ROS)之间的关系。我们发现，老化过程强烈地增强了核因子-kappa B的激活及其DNA结合活性，并增加了ROS状态。伴随着核因子-kappaB活性的改变，核蛋白p65蛋白的增加证实了ikappaBα的降低。因此，这些数据有力地表明，衰老过程通过下调I kappa Bα来增加NF-kappa B的活性。进一步的研究表明，年龄相关的氧化状态与COX衍生前列腺素生物合成过程的增加相关，是由NF-kappa B调节的COX活性增加所介导的。这种核因子-kappaB活性的增加伴随着COX-2mRNA和蛋白水平的增加。基于这些数据，我们得出结论，氧化还原敏感型核因子-kappa B移位和结合活性的年龄相关性增加与ROS的增加有关，而且这种反式激活受到与年龄相关的I kappa Bα减少的调节。(C)2000年爱思唯尔科学公司。
Increased oxidative stress resulting in the activation of NF-kappa B is thought to play a crucial role in the expression of the cyclooxygenase-2 (COX-2), which is the key enzyme in proinflammatory prostanoid synthesis. In the current study, we investigated whether the aging process affects the status of the redox-sensitive NF-kappa B in rat kidney, and how this age-related modulation is related to COX-2 gene expression and COX-derived reactive oxygen species (ROS). We found that the aging process strongly enhanced the activation of NF-kappa B and its DNA-binding activity with an increased ROS status. Accompanied with the change in the NF-kappa B activity was a decreased I kappa B alpha as confirmed by the increased nuclear p65 protein. Thus, these data strongly indicated that the aging process increases NF-kappa B activity by downregulating I kappa B alpha. A closer examination further revealed that age-related oxidative status correlated with the increased COX-derived prostanoid biosynthetic process is mediated by the increased NF-kappa B-regulated COX activity. This increase in NF-kappa B activity was accompanied by the increased COX-2 mRNA and protein levels. Based on these data, we concluded that the age-related increase in redox-sensitive NF-kappa B translocation and binding activities are associated with increased ROS, and further that this transactivation was modulated by the age-related decrease of I kappa B alpha. (C) 2000 Elsevier Science Inc.