Constitutive activity of NADPH oxidase 1 (Nox1) that promotes its own activity suppresses the colon epithelial cell migration

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 affe...

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Bibliographic Details
Published in:Free radical research 2020-09, Vol.54 (8-9), p.640-648
Main Authors: Miyano, Kei, Okamoto, Shuichiro, Yamauchi, Akira, Kajikawa, Mizuho, Kiyohara, Takuya, Taura, Masahiko, Kawai, Chikage, Kuribayashi, Futoshi
Format: Article
Language:English
Subjects:
cell migration
edaravone
epithelial cells
NADPH oxidase
NOX1
ROS
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Summary: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.
ISSN:1071-5762
1029-2470
DOI:10.1080/10715762.2020.1823383