Nuclear factor-kappaB mediates over-expression of cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency.
Nuclear factor-kappaB mediates over-expression of cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency.
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DOI：
10.1016/s0891-5849(02)00775-x
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发表时间：
2002-05
影响因子：
7.4
通讯作者：
Faith Zamamiri-Davis;Ying Lu;Jerry T. Thompson;K. Prabhu;Padala V Reddy;Lorraine M Sordillo;C. Reddy
中科院分区：
文献类型：
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作者：
Faith Zamamiri-Davis;Ying Lu;Jerry T. Thompson;K. Prabhu;Padala V Reddy;Lorraine M Sordillo;C. Reddy
硒（Se）是所有哺乳动物物种必需的微量营养素，并且以硒蛋白的形式与多种生理功能，特别是免疫系统相关。硒营养不足与各种疾病有关，包括类风湿性关节炎，心肌病和癌症。重要的是，环氧合酶-2（考克斯-2）在所有上述病理中过度表达，然而，硒状态和考克斯-2表达之间的因果关系仍有待建立。目前的研究是基于这样的假设，即氧化应激，硒缺乏的后果，降低氧化还原敏感的转录因子，NF-κB的活化潜力，并激活NF-κB是所需的考克斯-2的表达改变。为了验证这一假设，我们研究了硒状态和考克斯-2表达之间的关系，在RAW 264.7，巨噬细胞样细胞系的LPS刺激。在硒缺乏的细胞中，硒依赖性谷胱甘肽过氧化物酶活性（Se-GPx），硒状态的措施，显着降低，整体氧化应激显着高于硒补充细胞。在脂多糖（LPS）刺激下，我们发现缺硒细胞中考克斯-2蛋白表达和PGE 2水平比补硒细胞高2-3倍。相比之下，考克斯-1蛋白表达不受LPS刺激或硒状态的影响。在LPS刺激后，NF-κB在缺硒巨噬细胞中的核定位显著增加，从而导致考克斯-2表达增加。这是第一份证明硒状态和考克斯-2表达之间呈负相关关系的报告。
Selenium (Se) is an essential micronutrient for all mammalian species and is associated with a variety of physiological functions, notably immune system, in the form of selenoproteins. Inadequate Se nutrition has been linked to various diseases, including rheumatoid arthritis, cardiomyopathy, and cancer. Important to this discussion is that cyclooxygenase-2 (COX-2) is over-expressed in all the aforesaid pathologies; however, a casual relationship between Se status and COX-2 expression remains to be established. The present study is based on the hypothesis that oxidant stress, a consequence of Se deficiency, lowers the activation potential of the redox-sensitive transcription factor, NF-κB, and that the activated NF-κB is required for the altered expression of COX-2. To test this hypothesis, we have investigated the relationship between Se status and COX-2 expression in response to LPS stimulation in RAW 264.7, a macrophage-like cell line. In Se-deficient cells, the Se-dependent glutathione peroxidase activity (Se-GPx), a measure of Se status, was markedly reduced and the overall oxidative stress was significantly higher than Se-supplemented cells. Upon lipopolysaccharide (LPS) stimulation, we found 2-3-folds higher COX-2 protein expression as well as higher PGE2levels in Se-deficient cells than Se-supplemented cells. In comparison, COX-1 protein expression was not affected by either LPS stimulation or Se status. Following LPS stimulation, the nuclear localization of NF-κB was significantly increased in Se-deficient macrophages, thereby leading to increased expression of COX-2. This is the first report demonstrating an inverse relationship between Se status and the expression of COX-2.