Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because myotonic dystrophy (MD) is an autosomal dominant multisystemic disorder affecting plasma membrane, we have studied the oxidative burst of PMNs. The PMA and fMet-Leu-Phe-stimulated superoxide generation is defective in the patient group as compared to controls: the response is both delayed and low. The kinetic parameters of the NADPH oxidase complex are not affected. We have not found any abnormalities in the membrane potential changes. In addition, the cytosolic protein kinase C (PKC) activity of resting PMNs is similar in MD patients and controls, and the translocation of protein kinase C in response to PMA is not impaired. The decrease of the oxidative response of PMNs from MD patients may be related to an abnormality of the environment of the NADPH oxidase.
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PMID:Myotonic dystrophy: defective oxidative burst of polymorphonuclear leukocytes. 284 20

The superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytes (phox) plays a key role in production of reactive oxygen species (ROS) by microglia. The catalytic subunits of the NADPH oxidase are composed of p22phox and gp91phox. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. Pathologically, the brains of NHD patients exhibit extensive demyelination designated leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes. However, a pathological role of the gp91phox-p22phox complex in generation of leukoencephalopathy in NHD remains unknown. We clarified the expression of gp91phox and p22phox in the white matter of the frontal cortex derived from five NHD and eight control subjects. We identified the expression of p22phox and gp91phox immunoreactivity almost exclusively on microglia. Microglia overexpressed gp91phox in NHD brains and p22phox in myotonic dystrophy (MD) brains, when compared with non-neurological control (NC) brains. These results suggest that the enhanced expression of gp91phox by microglia might contribute to overproduction of ROS highly toxic to myelinating oligodendrocytes, resulting in oligodendrocyte cell death that induces leukoencephalopathy in NHD brains.
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PMID:Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains. 2790 23