Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation.
Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation.
复制标题
通过活性氧生成快速上调内皮 P-选择素表达。
DOI：
10.1152/ajpheart.01001.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Bulkley,GregoryB
中科院分区：
文献类型：
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作者：
Takano,Manabu;Meneshian,Avedis;Sheikh,Emran;Yamakawa,Yasuhiko;Wilkins,KirstenBass;Hopkins,EliseA;Bulkley,GregoryB
TNF-α诱导的内皮细胞ICAM-1上调部分由内皮膜相关NADPH氧化酶产生的活性氧（ROS）介导，并在4 h后最大程度地发生，因为需要合成新蛋白质。然而，凝血酶刺激的P-选择素上调是双峰的，第一个峰值出现在几分钟内。我们推测，这一早期的峰值，这是从内韦伯-帕拉德机构释放的预成型的P-选择素的结果，是介导的部分由ROS产生的内皮细胞膜相关的黄嘌呤氧化酶。我们发现，这种P-选择素在内皮细胞表面的快速表达伴随着ROS生成的定性平行增加。P-选择素的表达和ROS的产生都受到抑制，剂量依赖性，通过外源性施用不同的细胞渗透性抗氧化剂，也通过抑制已知的膜相关的ROS生成酶NADPH氧化酶或黄嘌呤氧化酶。这种快速的翻译后细胞信号传导反应，不仅由经典的NADPH氧化酶，但也由黄嘌呤氧化酶产生的ROS介导，很可能是一个重要的生理触发微血管炎症反应。
Endothelial cell ICAM-1 upregulation in response to TNF-α is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response.