Interaction between p22phox and Nox4 in the endoplasmic reticulum SUGGESTS A UNIQUE mechanism of NADPH oxidase complex formation.

Interaction between p22phox and Nox4 in the endoplasmic reticulum SUGGESTS A UNIQUE mechanism of NADPH oxidase complex formation.
Free Radic Biol Med. 2017 Dec 23;:
Authors: Zana M, Péterfi Z, Kovács HA, Tóth ZE, Enyedi B, Morel F, Paclet MH, Donkó Á, Morand S, Leto TL, Geiszt M
Abstract
The p22phox protein is an essential component of the phagocytic- and inner ear NADPH oxidases but its relationship to other Nox proteins is less clear. We have studied the role of p22phox in the TGF-β1-stimulated H2O2 production of primary human and murine fibroblasts. TGF-β1 induced H2O2 release of the examined cells, and the response was dependent on the expression of both Nox4 and p22phox. Interestingly, the p22phox protein was present in the absence of any detectable Nox/Duox expression, and the p22phox level was unaffected by TGF-β1. On the other hand, Nox4 expression was dependent on the presence of p22phox, establishing an asymmetrical relationship between the two proteins. Nox4 and p22phox proteins localized to the endoplasmic reticulum and their distribution was unaffected by TGF-β1. We used a chemically induced protein dimerization method to study the orientation of p22phox and Nox4 in the endoplasmic reticulum membrane. This technique is based on the rapamycin-mediated heterodimerization of the mammalian FRB domain with the FK506 binding protein. The results of these experiments suggest that the enzyme complex produces H2O2 into t...

Source: Free Radical Biology and Medicine - December 23, 2017 Category: Biology Authors: Zana M, Péterfi Z, Kovács HA, Tóth ZE, Enyedi B, Morel F, Paclet MH, Donkó Á, Morand S, Leto TL, Geiszt M Tags: Free Radic Biol Med Source Type: research