Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The topography of the inner mitochondrial membrane was investigated using inhibitors of electron transport on preparations of beef heart mitochondria and electron transport particles of opposite orientation. Reductions of juglone, ferricyanide, indophenol, coenzyme Q, duroquinone, and cytochrome c by NADH are inhibited to different extents on both sides of the membrane by the impermeant hydrophilic chelators bathophenanthroline sulfonate and orthophenanthroline. The extent of inhibition for each acceptor increased in the order given. At least two chelator-sensitive sites are present on each membrane face between the flavoprotein and coenzyme Q and a chelator-sensitive site is present on the matrix face between the sites of coenzyme Q and duroquinone interaction. Duroquinol oxidation in mitochondria only is stimulated by bathophenanthroline sulfonate. Juglone reduction is stimulated in electron transport particles (only) by p-hydroxymercuribenzenesulfonate, but after mercurial treatment, juglone reduction in both particles and mitochondria is more sensitive to bathophenanthroline sulfonate. Succinate dehydrogenase components are inhibited by hydrophilic orthophenanthroline or bathophenanthroline sulfonate in mitochondria only. Electron flow between the dehydrogenases of succinate and NADH occurs via a chelator-sensitive site located on the matrix face of the membrane. Inter-complex electron flow is prevented by rotenone or thenoyltrifluoroacetone. The lack of succinate-indophenol reductase inhibition by bathophenanthroline sulfonate in the presence of rotenone or thenoyltrifluoroacetone indicates that the rotenone-sensitive site may be located on the matrix face and demonstrates that electrons flow between the NADH and succinate dehydrogenases via a hydrophilic chelator and rotenone-thenoyltrifluoroacetone-sensitive site on the matrix face of the membrane. Inhibiton by hydrophilic chelators only in mitochondria indicates that succinate dehydrogenase as well as NADH dehydrogenase has a transmembranous orientation.
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PMID:Inhibition of mitochondrial electron transport by hydrophilic metal chelators. Determination of dehydrogenase topography. 94 64

Naturally occurring quinones and quinone-containing extracts of seeds of the toxic plant Cassia obtusifolia (sicklepod) affected muscle mitochondrial function. Aqueous suspensions and organic extracts of C. obtusifolia seeds slightly elevated plasma creatine kinase levels of Sprague-Dawley rats. These extracts were analyzed by fused silica capillary gas chromatography and found to contain nine anthraquinones and three anthrones. Urinary metabolites primarily consisted of beta-glucuronide conjugates of the anthraquinones. The three anthrones or conjugate analogues were not present in the urine in detectable amounts. Emodin, doxorubicin and organic extracts of C. obtusifolia inhibited NADH:cytochrome c oxidoreductase activity of bovine heart mitochondrial particles and NADH:CoQ oxidoreductase activity of porcine heart mitochondrial NADH dehydrogenase, whereas juglone was stimulatory. Relative quinone metabolism correlated with semiquinone formation rate and with redox potential. A protective effect of coenzyme Q against enzyme inhibition by anthraquinones was also observed.
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PMID:Effects of Cassia obtusifolia (sicklepod) extracts and anthraquinones on muscle mitochondrial function. 274 52

Nitroxides stable radicals are unreactive toward most diamagnetic molecules, but readily undergo one-electron redox reactions with paramagnetic species such as free radicals and transition metals, thus serving as cell-permeable antioxidants. The cytotoxicity of juglone (5-hydroxy-1,4-naphthoquinone), like that of other naphthoquinones, requires bioreduction to yield the semiquinone which in turn reduces oxygen to O2.-. Therefore, nitroxides are expected to mitigate cytotoxicity of quinone-based xenobiotics, such as naphthoquinones. In the present study, in vitro scission of isolated DNA was induced upon juglone reduction by glutathione and Fe(II) ions, however, not by xanthine oxidase or cytochrome c reductase. The DNA scission was inhibited by nitroxides, catalase and chelating agents, though not by superoxide dismutase. Juglone was more toxic toward bacterial cells under hypoxia than under air. Nitroxides < or = 2 mM protected bacterial cells from juglone-induced toxicity under both aerobic and hypoxic conditions. The cytoprotective effect of lipophilic nitroxide was greater than that of hydrophilic ones. Catalase and metal chelating agents decreased juglone-induced cell killing, whereas H2O2 increased it. The mechanisms underlying the nitroxides protective effect involve (a) the reoxidation of reduced transition metal ions, (b) the selective radical-radical reaction with juglone semiquinone, and possibly (c) under aerobic condition catalytic removal of extra- and intracellular O2.-. The present results suggest also that the cell membrane rather than DNA is the main target of juglone toxicity.
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PMID:Effects of nitroxide stable radicals on juglone cytotoxicity. 803 50

Photodynamic therapy (PDT) is a therapeutic modality used for the treatment of a variety of solid neoplasms. The principle of PDT is based on the selective uptake of a photosensitizing chemical in tumor tissue/cell followed by irradiation of tumors with visible light. The treatment results in a cascade of oxidative events causing cell death both in vitro and in vivo. Nitric oxide (NO) is a gaseous free radical, which is an important modulator of immune, endocrine and neuronal functions and plays an important role in the induction of apoptosis. Hypericin (HY) is a photosensitizing pigment from Hypericum perforatum that displays phototoxic effects in neoplastic cell lines. Our previous studies have shown HY induced apoptotic cell death in nasopharyngeal carcinoma and other tumor cells. To better understand the oxidative mechanism of apoptosis induced by HY, we hypothesized the role of NO in PDT, which is considered to be involved in a variety of physiological and pathological processes. We first demonstrated the presence of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) reactivity, a potential marker of NO synthesizing (NOS) enzyme both at light (LM) and electron microscopic (EM) level. Immunocytochemistry, using specific antibodies for NOS subtypes (constitutive, NOS I and inducible, NOS II), we observed that both NOS I and NOS II was present in all cell lines. The expression of both NOS I and NOS II was further verified using Western blot analysis as early as 15 min post PDT compared to that of drug-treated non-irradiated and light alone treated control cells. Our observation of NO production and distribution using the DAF-2 method is direct evidence of NO production in PDT-treated cells.
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PMID:Nitric oxide mediated photo-induced cell death in human malignant cells. 1263 64