Constitutive activity of NADPH oxidase 1 (Nox1) that promotes its own activity suppresses the colon epithelial cell migration
Constitutive activity of NADPH oxidase 1 (Nox1) that promotes its own activity suppresses the colon epithelial cell migration
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DOI：
10.1080/10715762.2020.1823383
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发表时间：
2020-09-25
影响因子：
3.3
通讯作者：
Kuribayashi, Futoshi
中科院分区：
文献类型：
--
作者：
Miyano, Kei;Okamoto, Shuichiro;Kuribayashi, Futoshi
超氧化物歧化产物NADPH氧化酶1(Nox1)在结肠上皮细胞中大量表达，在粘膜宿主防御中发挥重要作用。在这项研究中，我们发现，用自由基清除剂依达拉奉预处理细胞，即使在洗涤后也能抑制Nox1的构造活性，而不影响Nox1向质膜的转运和细胞质调节因子Noxo1和Noxa1的膜募集。这些结果表明，在形成Nox1-Noxo1-Noxa1络合物后，启动电子转移反应的步骤涉及Nox1衍生产物。此外，我们还发现抑制固有的Nox1活性显著提高了上皮细胞的平均迁移方向和迁移速度。因此，结构性的Nox1活性限制了静息细胞中不受欢迎的细胞迁移，同时参与了对自身氧化酶活性的正反馈循环。
Superoxide producing NADPH oxidase 1 (Nox1), abundantly expressed in the colon epithelium, plays a crucial role in mucosal host defenses. In this study, we found that pre-treatment of cells with edaravone, a free radical scavenger, inhibited Nox1 constitutive activity even after washout without affecting Nox1 trafficking to the plasma membrane and membrane recruitment of the cytosolic regulators Noxo1 and Noxa1. These results suggest that a Nox1-derived product is involved in the step that initiates the electron transfer reaction after the formation of the Nox1-Noxo1-Noxa1 complex. Furthermore, we show that the mean migration directionality and velocity of epithelial cells were significantly enhanced by the inhibition of constitutive Nox1 activity. Thus, the constitutive Nox1 activity limits undesired cell migration in resting cells while participating in a positive feedback loop toward its own oxidase activity.