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

  • Kei Miyano
    Department of Biochemistry, Kawasaki Medical School, Okayama, Japan
  • Shuichiro Okamoto
    Department of Biochemistry, Kawasaki Medical School, Okayama, Japan
  • Akira Yamauchi
    Department of Biochemistry, Kawasaki Medical School, Okayama, Japan
  • Mizuho Kajikawa
    Laboratory of Microbiology, Showa Pharmaceutical University, Machida, Japan
  • Takuya Kiyohara
    Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, Japan
  • Masahiko Taura
    Department of Otorhinolaryngology, Faculty of medicine, Fukuoka University, Fukuoka, Japan
  • Chikage Kawai
    Department of Biochemistry, Kawasaki Medical School, Okayama, Japan
  • Futoshi Kuribayashi
    Department of Biochemistry, Kawasaki Medical School, Okayama, Japan

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説明

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.

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