Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24386930
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Antioxid+Redox+Signal
2014 ; 20
(17
): 2755-75
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Nox NADPH oxidases and the endoplasmic reticulum
#MMPMID24386930
Laurindo FR
; Araujo TL
; Abrahão TB
Antioxid Redox Signal
2014[Jun]; 20
(17
): 2755-75
PMID24386930
show ga
SIGNIFICANCE: Understanding isoform- and context-specific subcellular Nox reduced
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase compartmentalization
allows relevant functional inferences. This review addresses the interplay
between Nox NADPH oxidases and the endoplasmic reticulum (ER), an increasingly
evident player in redox pathophysiology given its role in redox protein folding
and stress responses. RECENT ADVANCES: Catalytic/regulatory transmembrane
subunits are synthesized in the ER and their processing includes folding,
N-glycosylation, heme insertion, p22phox heterodimerization, as shown for
phagocyte Nox2. Dual oxidase (Duox) maturation also involves the regulation by
ER-resident Duoxa2. The ER is the activation site for some isoforms, typically
Nox4, but potentially other isoforms. Such location influences redox/Nox-mediated
calcium signaling regulation via ER targets, such as sarcoendoplasmic reticulum
calcium ATPase (SERCA). Growing evidence suggests that Noxes are integral
signaling elements of the unfolded protein response during ER stress, with Nox4
playing a dual prosurvival/proapoptotic role in this setting, whereas Nox2
enhances proapoptotic signaling. ER chaperones such as protein disulfide
isomerase (PDI) closely interact with Noxes. PDI supports growth factor-dependent
Nox1 activation and mRNA expression, as well as migration in smooth muscle cells,
and PDI overexpression induces acute spontaneous Nox activation. CRITICAL ISSUES:
Mechanisms of PDI effects include possible support of complex formation and
RhoGTPase activation. In phagocytes, PDI supports phagocytosis, Nox activation,
and redox-dependent interactions with p47phox. Together, the results implicate
PDI as possible Nox organizer. FUTURE DIRECTIONS: We propose that convergence
between Noxes and ER may have evolutive roots given ER-related functional
contexts, which paved Nox evolution, namely calcium signaling and pathogen
killing. Overall, the interplay between Noxes and the ER may provide relevant
insights in Nox-related (patho)physiology.
free
free
free
