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)

We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide (O2.-) generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herb Hypericin triquetrifolium Turra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on stimulation-dependent O2.- generation and related enzymes of neutrophils were investigated. Hypericin inhibited O2.- generation of neutrophils induced by PKC-dependent and -independent stimuli in a light- and concentration-dependent manner. Oxygen was required for the light-dependent inhibition by hypericin. NADPH oxidase activity in a cell-free system and TNF-alpha-induced tyrosyl phosphorylation of neutrophil proteins were also inhibited by hypericin in a concentration- and light-dependent manner. However, tyrosine kinase of p60src, an enzyme not bound to a membrane, was not inhibited either in the light or in the dark. Oxygen uptake of neutrophils by photosensitization with hypericin resulted in the formation of singlet oxygen (1O2), O2.-, and hydroxyl radical (.OH) and enhanced lipid peroxidation. The formation of 1O2 was inhibited by azide, a quencher of 1O2, but not by desferrioxamine (DSF), a ferric ion chelator. By contrast, both generation of .OH and lipid peroxidation were inhibited by DSF but not by azide. Furthermore, PMA-induced O2.- generation inhibited by hypericin partially recovered in the presence of azide but not DSF. These results suggested that the light-dependent inhibition of O2.- generation by hypericin might be due to inhibition of tyrosine kinase, PKC, and NADPH oxidase via an oxygen-dependent mechanism, possibly through both Type I and II photosensitization mechanisms.
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PMID:Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent. 748 96

Hypericin is a photosensitizing pigment found in St. John's wort (Hypericum perforatum) displaying a high toxicity towards certain tumors. The fact that some non-tumor cells, especially monocytes and granulocytes, are resistant to its photocytotoxic effects, posed the question whether this insensitivity is due to their ability to accumulate vitamin C, an antioxidant which alleviates the deleterious work of free radicals. HL-60 promyelocytic tumor cells can be differentiated to neutrophilic granulocytes by treatment with dimethylsulfoxide and were used as cell model. In the differentiated cells, treatment with phorbol esters (PMA) stimulates vitamin C (ascorbate) transport. The uptake rates were unaltered by hypericin at concentrations below 1 microM and irradiation with visible light at a light dose of 6 J/cm2. Inhibition by higher concentrations of hypericin was most probably due to a combination of photocytotoxic properties of the dye and oxygen radicals generated during respiratory burst. Superoxide production by NADPH oxidase followed by reduction of ferricytochrome c was inhibited by hypericin. The degree of inhibition was dependent on the concentration of hypericin and light intensity: IC50-values were 1.7 and 0.7 microM under light doses of 3.6 and 10.8 J/cm2, respectively. Oxidative stress, monitored with 2',7'-dichlorofluorescein (DCF) was only slightly decreased by ascorbate even at higher concentrations of hypericin. In contrast to its effect on the ferricytochrome c-reduction, irradiation had no significant influence on DCF-fluorescence. However, the viability of the cells was strongly decreased after photosensitization and no significant improvement was obtained by ascorbate. Results from this work indicate that ascorbate transport per se is not altered during photodynamic therapy and vitamin C does not interfere with hypericin-induced photodamage of cellular targets.
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PMID:Hypericin and photodynamic treatment do not interfere with transport of vitamin C during respiratory burst. 1551 95

Heat shock (HS, 40 degrees C, 10 min) induces hypericin production, nitric oxide (NO) generation, and hydrogen peroxide (H(2)O(2)) accumulation of Hypericum perforatum suspension cells. Catalase (CAT) and NO specific scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) suppress not only the HS-induced H(2)O(2) generation and NO burst, but also the HS-triggered hypericin production. Hypericin contents of the cells treated with both NO and H(2)O(2) are significantly higher than those of the cells treated with NO alone, although H(2)O(2) per se has no effects on hypericin production of the cells, which suggests the synergistic action between H(2)O(2) and NO on hypericin production. NO treatment enhances H(2)O(2) levels of H. perforatum cells, while external application of H(2)O(2) induces NO generation of cells. Thus, the results reveal a mutually amplifying action between H(2)O(2) and NO in H. perforatum cells. CAT treatment inhibits both HS-induced H(2)O(2) accumulation and NO generation, while cPTIO can also suppress H(2)O(2) levels of the heat shocked cells. The results imply that H(2)O(2) and NO may enhance each other's levels by their mutually amplifying action in the heat shocked cells. Membrane NAD(P)H oxidase inhibitor diphenylene iodonium (DPI) and nitric oxide synthase (NOS) inhibitor S,S'-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea (PBITU) not only inhibit the mutually amplifying action between H(2)O(2) and NO but also abolish the synergistic effects of H(2)O(2) and NO on hypericin production, showing that the synergism of H(2)O(2) and NO on secondary metabolite biosynthesis might be dependent on their mutual amplification. Taken together, data of the present work demonstrate that both H(2)O(2) and NO are essential for HS-induced hypericin production of H. perforatum suspension cells. Furthermore, the results reveal a special interaction between the two signal molecules in mediating HS-triggered secondary metabolite biosynthesis of the cells.
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PMID:Signal interaction between nitric oxide and hydrogen peroxide in heat shock-induced hypericin production of Hypericum perforatum suspension cells. 1867 95