The NADPH oxidase of professional phagocytes—prototype of the NOX electron transport chain systems

Cross, Andrew R.; Segal, Anthony W.

doi:10.1016/j.bbabio.2004.03.008

Cited by 415 publications

(339 citation statements)

References 343 publications

(461 reference statements)

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“…[51] Therefore, increases in Nox2 levels in mdx skeletal muscle are likely related to inflammatory responses associated with muscle cell death and regeneration. In a study using Nox2 (gp91phox) deficient mice, a 90% reduction in the number of muscle fibers showing extensive membrane injury was found compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Spurney

Knoblach

Pistilli

et al. 2008

Neuromuscular Disorders

137

133

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Duchenne muscular dystrophy (DMD; dystrophin-deficiency) causes dilated cardiomyopathy in the second decade of life in affected males. We studied the dystrophin-deficient mouse heart (mdx) using high frequency echocardiography, histomorphometry, and gene expression profiling. Heart dysfunction was prominent at 9-10 months of age and showed significantly increased LV internal diameter (end systole) and decreased posterior wall thickness. This cardiomyopathy was associated with a 30% decrease in shortening fraction. Histologically, there was a 10-fold increase in connective tissue volume (fibrosis). mRNA profiling with RT-PCR validation showed activation of key profibrotic genes, including Nox4 and Lox. The Nox gene family expression differed in mdx heart and skeletal muscle, where Nox2 was specifically induced in skeletal muscle while Nox4 was specifically induced in heart. This is the first report of an altered profibrotic gene expression profile in cardiac tissue of dystrophic mice showing echocardiographic evidence of cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Spurney

Knoblach

Pistilli

et al. 2008

Neuromuscular Disorders

137

133

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“…The activation of NADPH oxidase requires the assembly of membrane bound flavocytochrome b 558 with the cytosolic components p47 phox , p67 phox , p40 phox and rac 2 [20]. Having identified proteins homologous to p47 phox and p67 phox in insect hemocytes by MALDI-TOF [6], experiments were undertaken to investigate whether these homologous proteins also transferred from the cytosolic compartment to the membrane fraction as a result of cellular activation.…”

Section: Membrane Translocation Of Cytosolic Protein Homologous To P4mentioning

confidence: 99%

“…The O 2 À generating NADPH oxidase is a multicomponent system consisting of a membrane-bound flavocytochrome b 558 (composed of two subunits, p22 phox and gp91 phox ) [19] and four cytosolic factors, p47 phox , p67 phox , p40 phox and the small G protein, rac 2 [20]. These cytosolic proteins interact with each other [21,22], with rac [23,24] and with the flavocytochrome [25][26][27] through a number of Src homology 3 (SH3), proline-rich, tetratricopeptide repeat, and PC motifs.…”

Section: Introductionmentioning

confidence: 99%

Translocation of proteins homologous to human neutrophil p47phox and p67phox to the cell membrane in activated hemocytes of Galleria mellonella

Renwick

Reeves

Wientjes

et al. 2007

Developmental & Comparative Immunology

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Activation of the superoxide forming respiratory burst oxidase of human neutrophils, crucial in host defence, requires the cytosolic proteins p47 phox and p67 phox which translocate to the plasma membrane upon cell stimulation and activate flavocytochrome b 558 , the redox centre of this enzyme system. We have previously demonstrated the presence of proteins (67 and 47 kDa) in hemocytes of the insect Galleria mellonella homologous to proteins of the superoxide-forming NADPH oxidase complex of neutrophils. The work presented here illustrates for the first time translocation of homologous hemocyte proteins, 67 and 47 kDa from the cytosol to the plasma membrane upon phorbol 12-myristate 13 acetate (PMA) activation. In hemocytes, gliotoxin (GT), the fungal secondary metabolite significantly suppressed PMA-induced superoxide generation in a concentration dependent manner and reduced translocation to basel nonstimulated levels. Primarily these results correlate translocation of hemocyte 47 and 67 kDa proteins with PMA induced oxidase activity. Collectively results presented here, demonstrate further cellular and functional similarities between phagocytes of insects and mammals and further justify the use of insects in place of mammals for modelling the innate immune response to microbial pathogens. r

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“…NADPH oxidase is composed of cytosolic component, including p47 phox , p67 phox , Rac-1, and a membrane component, such as gp91 phox (43,44). This enzyme produces O 2 2 and O 2 2 -derived oxidants through translocation of its subunits from the cytosol to plasma membrane in activated glial cells, which eventually contributes to DA neuronal death in MPTP-treated mice (4).…”

Section: Win55212-2 Inhibits Mptp-induced Activation Of Microglial Nmentioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

111

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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The NADPH oxidase of professional phagocytes—prototype of the NOX electron transport chain systems

Cited by 415 publications

References 343 publications

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Translocation of proteins homologous to human neutrophil p47phox and p67phox to the cell membrane in activated hemocytes of Galleria mellonella

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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