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Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based reactive oxygen species generation and cell migration: collaboration of oxidant generating and scavenging systems.

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Kwon J, Burke DJ, Wang A, Boudreau HE, Lekstrom KJ, Korzeniowska A, Kim YS, Li L, Bunyak F, Jaeger S, Palaniappan K, Ambruso DR, Jackson SH, Leto TL
NIH Research Festival 2014.
Abstract: 

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family that exhibits 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 ROS release. Prdx6-dependent enhanced ROS production by Nox1 depends on both the peroxidase and phospholipase A2 activities of Prdx6, since peroxidase and lipase-deficient mutant forms failed to bind to or stabilize Nox1 components or support Nox1- mediated ROS generation. Furthermore, Wild-type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which an antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing.

Kwon J, Burke DJ, Wang A, Boudreau HE, Lekstrom KJ, Korzeniowska A, Kim YS, Li L, Bunyak F, Jaeger S, Palaniappan K, Ambruso DR, Jackson SH, Leto TL. Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based reactive oxygen species generation and cell migration: collaboration of oxidant generating and scavenging systems. NIH Research Festival 2014.