HUGO ID Detailed Result 14874

HUGO ID 14874
Symbol NOX5
Name NADPH oxidase, EF-hand calcium binding domain 5
#Occurrence 54
#Paper 5

 

PMID Match String Actual String Score Flanking text Edited by Edit
18219386NOX5Nox50.9The Nox family is composed of 7 members Nox1_amp_#x02013 Nox5 Duox1 and Duox2 are distributed in a variety of tissues 
18219386NOX5Nox50.9endothelial cells Nox4 in astrocytes neurons and endothelial cells and Nox5 in endothelial cells moreover high doses of apocynin have been 
18219386NOX5NOX50.9moreover high doses of apocynin have been reported to inhibit Nox4 and Nox5 ( 15 
18219386NOX5Nox50.9doses of apocynin have been reported to inhibit Nox4 and Nox5 ( 15 
16227974nadph oxidasenadph oxidase1.0a number of groups have proposed that a plasma membrane superoxide generating enzyme system known as the nadph oxidase is involved 22 .  
16227974nadph oxidasenadph oxidase1.0subsequent analysis showed that components of the nadph oxidase system are expressed in other cell types and that a large family of tissue specific oxidases exist 23 .  
16227974nadph oxidasenadph oxidase1.0consistent with its potential role in vascular disease knockout mice that are deficient in nadph oxidase have reduced vascular oxidant production and in some settings reduced atherosclerosis 24 25 .  
16877542nadph oxidasenadph oxidase1.0herein we show that nadph oxidase the main reactive oxygen species producing enzyme during inflammation is activated in spinal cords of als patients and in spinal cords in a genetic animal model of this disease.  
16877542nadph oxidasenadph oxidase1.0we demonstrate that inactivation of nadph oxidase in als mice delays neurodegeneration and extends survival.  
16877542nadph oxidasenadph oxidase1.0we also show that nadph oxidase derived oxidant products damage proteins such as insulin like growth factor 1 igf1 receptors which are located on motor neurons.  
16877542nadph oxidasenadph oxidase1.0nadph oxidase is up regulated in inflamed spinal cords of als mice.  
16877542nadph oxidasenadph oxidase1.0to determine the role of nadph oxidase in motor neuron degeneration we first evaluated its expression at different stages of the disease in transgenic mice expressing mutant human sod1 with a substitution of glycine to alanine in position 
16877542nadph oxidasenadph oxidase1.0expression of nadph oxidase in the spinal cord which carries the brunt of the pathology in this als model was determined by analyzing its catalytic subunit gp91 phox .  
16877542nadph oxidasenadph oxidase1.0the levels of the p67 phox subunit that contains the nadph binding site of the nadph oxidase complex 10 were increased in membrane fractions of spinal cord extracts from symptomatic transgenic sod1 g93a mice fig 1 c indicating that this cytosolic subunit did translocate to the plasma membran 
16877542nadph oxidasenadph oxidase1.0conversely none of these nadph oxidase alterations were seen in age matched nontransgenic littermates fig 1 a _amp_#x02013; e .  
16877542nadph oxidasenadph oxidase1.0consistent with nadph oxidase expression by professional phagocytes confocal microscopy demonstrated the colocalization of the gp91 phox subunit with a microglial marker the ricinus communis agglutinin lectin fig 1 h _amp_#x02013 
16877542nadph oxidasenadph oxidase1.0nadph oxidase causes protein oxidation in transgenic sod1 g93a mice.  
16877542nadph oxidasenadph oxidase1.0we further characterized the status of spinal cord nadph oxidase in transgenic sod1 g93a mice by probing for formation of ros and evidence of protein oxidation.  
16877542nadph oxidasenadph oxidase1.0nadph oxidase induction and neuronal protein carbonylation in sporadic als.  
16877542nadph oxidasenadph oxidase1.0we then sought to determine whether the nadph oxidase alterations identified in transgenic sod1 g93a mice were also present in human sporadic als the most common form of the disease 1 .  
16877542nadph oxidasenadph oxidase1.0next we explored the contribution of nadph oxidase activation on the disease phenotype in the sod1 g93a mouse model of als.  
16877542nadph oxidasenadph oxidase1.0in addition to the prolonged survival inactivation of nadph oxidase did mitigate neurodegeneration.  
16877542nadph oxidasenadph oxidase1.0nadph oxidase impairs the insulin like growth factor 1 igf1 /akt pathway in transgenic sod1 g93a mice.  
16877542nadph oxidasenadph oxidase1.0we then explored whether nadph oxidase mediated protein modifications might promote neurodegeneration in als by damaging essential surviving pathways for motor neurons such as igf1.  
16877542nadph oxidasenadph oxidase1.0to test the idea that nadph oxidase derived ros could impair igf1 pathway function an in vitro cell system using the neuron like cell lines sh sy5y and imr32 was used.  
16877542nadph oxidasenadph oxidase1.0however both the alteration of igf1 mediated akt phosphorylation and the loss of cell viability mediated by lps activated microglia were counteracted by the specific nadph oxidase inhibitor apocynin fig 5 c d and f .  
16877542nadph oxidasenadph oxidase1.0germane to the molecular basis of this deleterious effect on motor neurons is our finding that virtually all spinal cord microglial cells express the gp91 phox subunit of the oxidant producing enzyme nadph oxidase fig 1 .  
16877542nadph oxidasenadph oxidase1.0agreeing with the fact that in nonactivated phagocytes nadph oxidase is quiescent 7 gp91 phox positive cells in spinal cords from 1 to 4 month old nontransgenic mice had a morphology of resting microglia and did not seem to produce ros figs 1 and 6 .  
16877542nadph oxidasenadph oxidase1.0conversely in transgenic sod1 g93a mice paralleling the worsening of the als phenotype there was an intensification of spinal cord microgliosis accompanied by an up regulation and activation of nadph oxidase.  
16877542nadph oxidasenadph oxidase1.0corroborating this view are the levels of protein carbonyls which were markedly elevated in spinal cord extracts of symptomatic transgenic sod1 g93a mice for the most part in a nadph oxidase dependent manner fig 1 .  
16877542nadph oxidasenadph oxidase1.0evidence of microgliosis nadph oxidase up regulation and protein carbonylation was also found in postmortem spinal cords from human sporadic als cases fig 2 supporting the conclusion that the occurrence of inflammation mediated oxidative  
16877542nadph oxidasenadph oxidase1.0our results also show that abrogation of the gp91 phox subunit of nadph oxidase in transgenic sod1 g93a mice eliminates the production of microglial derived ros fig 1 m and importantly prolongs survival and retards neurodegeneration in this als model fig 3 .  
16877542nadph oxidasenadph oxidase1.0consequently the attenuated phenotype seen in transgenic sod1 g93a /gp91 phox_amp_#x02212; mice is attributable to the lack of nadph oxidase activity and not to either an impaired microglial response or expression of the human sod1 g93a transgene.  
16877542nadph oxidasenadph oxidase1.0these data provide compelling evidence that nadph oxidase contributes to the degeneration of motor neurons in als.  
16877542nadph oxidasenadph oxidase1.0however the magnitude of benefit afforded by gp91 phox deletion in transgenic sod1 g93a mice argues that targeting neuroinflammation by inhibiting just one of its mediators such as nadph oxidase may not be sufficient to produce robust and lasting neuroprotection in als patients.  
16877542nadph oxidasenadph oxidase1.0all cells not motor neurons only which are located in the vicinity of activated microglia may indiscriminately have their plasma membrane proteins and lipids damaged by nadph oxidase derived ros.  
16877542nadph oxidasenadph oxidase1.0in this study we indeed found that receptors for igf1 were primarily expressed on motor neurons in mouse spinal cords fig 8 and that the igf1 signaling pathway was impaired by a nadph oxidase dependent mechanism in symptomatic transgenic sod1 g93a mice fig 4 .  
16877542nadph oxidasenadph oxidase1.0although igf1 per se did not seem to be damaged by inflammation nadph oxidase did stimulate the oxidative modification of igf1 receptors fig 4 .  
16877542nadph oxidasenadph oxidase1.0ggregate show that several molecular events that are normally elicited by ligation of the igf1 receptor including autophosphorylation and akt phosphorylation were indeed abated by ros in a microglial nadph oxidase dependent manner.  
16877542nadph oxidasenadph oxidase1.0our data also show that microglial nadph oxidase by impairing the igf1 signaling pathway renders sh sy5y cells in our in vitro system more prone to die upon exposure to a hostile environment such as that emulated by lps activated microglial conditi 
16877542nadph oxidasenadph oxidase1.0in our study however we did not find any evidence that the rescue of the igf1 pathway by abrogating nadph oxidase was associated with muscle hypertrophy fig 3 .  
16877542nadph oxidasenadph oxidase1.0microglial nadph oxidase stimulates carbonylation of spinal cord motor neurons in transgenic sod1 g93a mice.  
16877542nadph oxidasenadph oxidase1.0nadph oxidase is up regulated and associated with motor neuron carbonylation in the spinal cord of sporadic als patients.  
16877542nadph oxidasenadph oxidase1.0modulation of the igf1/akt pathway by nadph oxidase derived ros.  
16877542nadph oxidasenadph oxidase1.0among the microglia derived mediators that could promote neurodegeneration are reactive oxygen species ros produced by the enzyme nadph oxidase complex 7 .  
16877542nadph oxidasenadph oxidase1.0in light of these facts we undertook the study of nadph oxidase in both human als and one of its genetic models.  
16877542nadph oxidasenadph oxidase1.0our results for both human and mouse postmortem tissues indicate that spinal cord microgliosis in als is accompanied with an up regulation of nadph oxidase.  
16877542nadph oxidasenadph oxidase1.0furthermore by using mutant deficient mice in functional nadph oxidase as well as in neuron like cell culture systems we provide compelling evidence that supports the concept that this microglial ros generating enzymatic complex promotes spinal cord motor neuron degener 
17105868nadph oxidasenadph oxidase1.0neurotrophins can induce oxidative stress through up regulation of nadph oxidase leading to neuronal cell necrosis kim et al. 2002 kim et al. 2002 .  
17956327nadph oxidasenadph oxidase1.0ros are continuously generated in cells through enzymatic e.g nadph oxidase and xanthine oxidase and non enzymatic e.g mitochondrial electron transport chain and receptor activation processes [ 46 ].  
17956327nadph oxidasenadph oxidase1.0nadph oxidase may generate the ros necessary for pltf since apocynin an nadph oxidase and superoxide anion inhibitor blocks pltf [ 24 ].  
17956327nadph oxidasenadph oxidase1.0indeed putative phrenic motor neurons and nearby astrocytes express subunits of the nadph oxidase complex i satriotomo p.m macfarlane d.j harrigan and g.s mitchell unpublished work .  
18219386nadph oxidasenadph oxidase1.0in this issue of the jci harraz and colleagues demonstrate that sod1 mutants expressed in human cell lines directly stimulate nadph oxidase nox by binding to rac1 resulting in overproduction of damaging ros see the related article beginning on page 659 .  
18219386nadph oxidasenadph oxidase1.0footnotes nonstandard abbreviations used: als amyotrophic lateral sclerosis; nox nadph oxidase; o 2 _amp_#x02022;_amp_#x02013; superoxide; sod1 superoxide dismutase_amp_#x02013;1.