Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based reactive oxygen species generation and cell migration.

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NIAID	MOLBIO-12

Authors

• J. Kwon
• D.J. Burke
• A. Wang
• H.E. Boudreau
• A. Korzeniowska
• Y.S. Kim
• L. Li
• S. Jaeger
• K. Palaniappan
• S.H. Jackson
• T.L. Leto

Abstract

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium that was proposed to function in epithelial homeostasis and wound healing. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the SH3 domain of Noxa1 as bait. Prdx6 is a unique member of the peroxiredoxin antioxidant enzyme family possessing both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild-type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-based reactive oxygen species (ROS) release. The Nox1-supportive function of Prdx6 depends on both its peroxidase and phospholipase activities, since the peroxidase and lipase-deficient mutant forms of Prdx6 failed to bind to and stabilize Nox1 components or support Nox1-mediated ROS generation and cell migration in an HCT-116 colon epithelial model of wound closure. These findings highlight a novel pathway in which an antioxidant enzyme can positively regulate an oxidant-generating system to support cell migration and wound healing.

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