A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and ERp72

2008 ◽  
Vol 416 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Wei Chen ◽  
Wei Hao Shang ◽  
Yoshifumi Adachi ◽  
Kunitaka Hirose ◽  
David M. Ferrari ◽  
...  

Emerging evidence indicates that Nox (NADPH oxidase) 1-generated ROS (reactive oxygen species) play critical regulatory roles in various cellular processes, yet little is known of direct targets for the oxidase. In the present study we show that one of the proteins selectively oxidized in response to Nox1-generated ROS was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology domains. Oxidation of ERp72 by Nox1 resulted in an inhibition of its reductase activity. EGF treatment of cells stimulated the Nox1 activity and the activated Nox1 subsequently mediated EGF-induced suppression of the ERp72 reductase activity. Co-immunoprecipitation, GST (glutathione transferase) pulldown assays and mutational analysis, indicated that Nox1 associates with ERp72, which involves its N-terminus encompassing a Ca2+-binding site and the first TRX-like motif. Furthermore, confocal microscopy showed co-localization between Nox1 and ERp72 at the plasma membrane. These results suggest that Nox1 functionally associates with ERp72, regulating redox-sensitive signalling pathways in a cellular context.

2006 ◽  
Vol 34 (5) ◽  
pp. 960-964 ◽  
Author(s):  
R. Dworakowski ◽  
N. Anilkumar ◽  
M. Zhang ◽  
A.M. Shah

Increased oxidative stress plays an important role in the pathophysiology of many diseases such as atherosclerosis, diabetes mellitus, myocardial infarction and heart failure. In addition to the well-known damaging effects of oxygen-free radicals, ROS (reactive oxygen species) also have signalling roles, acting as second messengers that modulate the activity of diverse intracellular signalling pathways and transcription factors, thereby inducing changes in cell phenotype. NADPH oxidases appear to be especially important sources of ROS involved in redox signalling. Seven NADPH oxidase isoforms, known as Noxs (NAPDH oxidases), are expressed in a cell- and tissue-specific fashion. These oxidases are thought to subserve distinct functions as a result of their tightly regulated activation (e.g. by neurohormonal and growth factors and mechanical stimuli) and their specific coupling with distinct downstream signalling pathways. In the present paper, we review the structure and mechanisms of activation of NADPH oxidases and consider their involvement in redox signalling, focusing mainly on the cardiovascular system.


2012 ◽  
Vol 142 (5) ◽  
pp. S-731
Author(s):  
Masashi Yasuda ◽  
Shinichi Kato ◽  
Naoki Yamanaka ◽  
Maho Iimori ◽  
Kazumi Iwata ◽  
...  

2009 ◽  
Vol 11 (9) ◽  
pp. 2105-2118 ◽  
Author(s):  
Ana Clara Cristóvão ◽  
Dong-Hee Choi ◽  
Graça Baltazar ◽  
M. Flint Beal ◽  
Yoon-Seong Kim

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