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Abstract
Novel function of NADPH oxidase in cell signaling: Applications for atherosclerosis and
drug discovery
Yun Soo Bae
Department of Life Science, Ewha Womans University
Reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, are
generally considered cytotoxic. However, many reports have demonstrated that intracellular
ROS, produced in mammalian cells in response to the activation of various receptors, serve as
important second messengers in cell signaling. Recently we reported that NADPH oxidase
(Nox) isozymes can be activated by toll-like receptors (TLRs), which are key regulators of
innate immunity. TLRs recognize pathogen-associated molecular patterns (PAMPs) on the
surface of pathogens as well as altered host proteins and lipoproteins and stimulate
inflammatory signaling pathways. We showed that the stimulation of TLR4 complex with
LPS as exogenous agonist or mmLDL as endogenous ligand induces reactive oxygen species
(ROS) generation and NF-κB activation and that this process is mediated by the regulation of
Nox isozymes. Moreover, we demonstrated that Nox-dependent ROS generation plays an
important role in LPS- and mmLDL-induced proinflammatory cytokine production by
endothelial cells (EC) and macrophages, respectively, leading to adhesion molecule
expression on surface of EC and migration of vascular cells. These results suggest that ROS
generated in response to TLR activation may play an important role in the process of
inflammation processes because infiltration of blood vessel by leukocytes, aided by the
expression of chemokines and adhesion molecules, is an initial and rate-limiting step in the
development of inflammation lesions. To extend this research, we investigated molecular
connections between TLR isotypes and Nox isozymes. In this seminar, I will introduce and
discuss the activation patterns of Nox isozymes by TLRs and its pathological events.