Evidence That Reactive Oxygen Species Do Not Mediate NF-kappaB Activation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 Jul 4

PMID 12839997

Citations 115

Authors

Makio Hayakawa

Hiroshi Miyashita

Isao Sakamoto

Masatoshi Kitagawa

Hirofumi Tanaka

Hideyo Yasuda

Michael Karin

Kiyomi Kikugawa

Affiliations

Soon will be listed here.

Abstract

It has been postulated that reactive oxygen species (ROS) may act as second messengers leading to nuclear factor (NF)-kappaB activation. This hypothesis is mainly based on the findings that N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), compounds recognized as potential antioxidants, can inhibit NF-kappaB activation in a wide variety of cell types. Here we reveal that both NAC and PDTC inhibit NF-kappaB activation independently of antioxidative function. NAC selectively blocks tumor necrosis factor (TNF)-induced signaling by lowering the affinity of receptor to TNF. PDTC inhibits the IkappaB-ubiquitin ligase activity in the cell-free system where extracellular stimuli-regulated ROS production does not occur. Furthermore, we present evidence that endogenous ROS produced through Rac/NADPH oxidase do not mediate NF-kappaB signaling, but instead lower the magnitude of its activation.

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