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)

MnCl2 induced manganese-containing superoxide dismutase (MnSOD) expression (mRNA, immunoreactive protein, and enzyme activity) in human breast cancer Hs578T cells. The induction of MnSOD immunoreactive protein in Hs578T cells was inhibited by tiron (a metal chelator and superoxide scavenger), pyruvate (a hydrogen peroxide scavenger), or 2-deoxy-d-glucose (DG, an inhibitor of glycolysis and the hexose monophosphate shunt), but not by 5,5-dimethyl-1-pyrroline-1-oxide (a superoxide scavenger), N-acetyl cysteine (a scavenger for reactive oxygen species and precursor of glutathione), diphenylene iodonium (an inhibitor of flavoproteins such as NADPH oxidase and nitric oxide synthase), or SOD (a superoxide scavenger). Northern blotting demonstrated that tiron or DG affected at the mRNA level, while pyruvate affected Mn-induced MnSOD expression at both the mRNA and protein levels. These results demonstrate that Mn can induce MnSOD expression in cultured human breast cancer cells. Mn also induced apoptosis and necrosis in these cells. Since inhibitors of Mn-induced MnSOD induction did not affect cell viability, MnSOD induction is probably not the cause of the Mn-induced cell killing.
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PMID:Induction of superoxide dismutase and cytotoxicity by manganese in human breast cancer cells. 1032 27

The oncogenic ras protein controls signal-transduction pathways that are critical for cell proliferation and tumorigenesis. Here, we demonstrate that v-Ha-ras-transduced human keratinocyte HaCaT cells produced significantly larger amounts of superoxide than did control cell lines. The superoxide generation was mediated by the transduced ras protein, because superoxide generation was modified by an inhibitor, lovastatin, that inhibits ras farnesylation during ras protein maturation. Superoxide generation was also inhibited by diphenylene iodonium, an inhibitor of flavoproteins, including NADPH oxidase, but not by rotenone, an inhibitor of the respiratory chain of the mitochondria. Those observations suggested that a phagocytic-like NADPH oxidase exists in keratinocytes that could be activated by the dominant activated v-Ha-ras and produce superoxide. Overexpression of manganese-containing superoxide dismutase and copper and zinc-containing superoxide dismutase cDNA via adenovirus infection also attenuated superoxide generation. Previous work has demonstrated that extracellular superoxide dismutase (SOD) can lower superoxide generation; this is the first report that intracellular SOD could also modify the amount of superoxide production from the cells. This report implies that superoxide radical may act as a second messenger molecule of oncogenic ras.
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PMID:Superoxide generation in v-Ha-ras-transduced human keratinocyte HaCaT cells. 1055 93

1. Overproduction of superoxide anions in the vascular wall contributes to endothelial dysfunction in vascular disease. A superoxide-generating reduced beta-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has recently been identified as a major source of oxidative radicals in vascular tissues. We studied the effects of a synthetic manganese-containing superoxide dismutase (SOD) mimetic, M40403, on NADPH oxidase-dependent superoxide generation and on endothelial dysfunction. 2. In rat aortic smooth muscle cells, NADPH (100 micro M) markedly stimulated superoxide production as detected by lucigenin (5 micro M)-enhanced chemiluminescence. M40403 reduced NADPH oxidase-dependent superoxide production in a concentration-dependent manner, with IC(50) being 31.6 micro M. In contrast, native Cu/Zn SOD (up to 300 U ml(-1)) had no effect. Angiotensin II (100 nM) increased the NADPH oxidase activity by 70%, and treatment with M40403 (10 micro M) reduced this increased superoxide to the control level. 3. In aortae from apolipoprotein(E)-deficient mice (apoE(0)) with hyperlipidemia and atherosclerosis, superoxide production is largely derived from NADPH oxidase. The attenuation of endothelial nitric oxide vasodilator function parallels the increase in vascular superoxide production at different stages of the disease. Acute incubation of such aortic rings with M40403 significantly suppressed superoxide production and improved endothelium-dependent vasorelaxation to a level comparable to that in wildtype control mice. 4. In summary, the cell-permeable SOD mimetic M40403 was found to reverse endothelial dysfunction in apoE(0) aorta ex vivo by decreasing NADPH oxidase-dependent superoxide levels. The advantages of synthetic SOD mimetics over the native Cu/Zn SOD enzyme, such as greater cell permeability and stability, confer significant therapeutic potential in vascular disease.
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PMID:Superoxide dismutase mimetic M40403 improves endothelial function in apolipoprotein(E)-deficient mice. 1287 23

Increased oxidative stress in adipocytes causes dysregulated expression of inflammation-related adipokines. We have examined the effects of exercise training on oxidative stress in rat white adipose tissue (WAT), especially focusing on inflammation-related adipokines. The levels of lipid peroxidation in WAT of exercise-trained (TR) rats were lower than those in control (C) rats. The content of manganese-containing superoxide dismutase in WAT of TR rats was increased as compared with those in C rats. In contrast, the expression of the NADPH oxidase NOX2 protein in WAT was downregulated by exercise training. Moreover, the levels of inflammation-related adipokines, such as tumor necrosis factor-alpha and monocyte chemoattractant protein-1, in WAT of TR rats were lower than those in C rats. The effects of exercise training were more remarkable in visceral WAT than in subcutaneous. These results suggest that exercise training decreases the expression of inflammation-related adipokines by reducing oxidative stress in WAT.
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PMID:Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. 1912 29