Disease relevance of iodanium

• Reactive oxygen species are the intracellular link in this process: phagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase [1].
• Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia [2].
• Overexpression of the FAD-binding domain of the sulphite reductase flavoprotein component from Escherichia coli and its inhibition by iodonium diphenyl chloride [3].
• In each case, the response to hypoxia was specifically inhibited by low doses of diphenylene iodonium (Ph1I+) [4].
• Iodonium ion-assisted synthesis of a haptenic tetrasaccharide fragment corresponding to the inner cell-wall glycopeptidolipid of Mycobacterium avium serotype 4 [5].

High impact information on iodanium

• Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages [6].
• Oxidation of TM by PMN is inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase [7].
• Hydrogen peroxide (H(2)O(2); 0.25 mM), a reactive oxygen species generated by functional NADPH oxidase, augmented K(+) current by >30% in both WT and OD cells; further, in WT cells, H(2)O(2) restored K(+) current amplitude in the presence of diphenylene iodonium [8].
• Superoxide dismutase as well as iodonium diphenyl, Ro 31-8220, and wortmannin attenuated PDGF-AB-induced activation of NF-kappaB and expression of MCP-1 mRNA [9].
• Inhibition of elicitor-stimulated ROS production using diphenylene iodonium blocked defense gene activation and phytoalexin accumulation [10].

Chemical compound and disease context of iodanium

• The NADPH oxidase inhibitors diphenylene iodonium (10microM) and phenylarsine oxide (5microM) were without effect on either basal Ca(2+) currents or responses to hypoxia [11].

Biological context of iodanium

• In the present study we followed O(2)(*-) production, changes of membrane potential, K(+) efflux, and bacterial killing in the presence of increasing concentrations of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium [12].
• We identified an Arabidopsis thaliana azide-sensitive but diphenylene iodonium-insensitive apoplastic oxidative burst that generates H(2)O(2) in response to a Fusarium oxysporum cell-wall preparation [13].
• Since inhibition of the mitochondrial respiratory chain has been shown to induce superoxide production and apoptosis, we investigated the effect of iodonium compounds on mitochondria-derived superoxide and apoptosis [14].
• Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect [15].
• Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2 [16].

Anatomical context of iodanium

• At the start of reoxygenation, the addition of diphenyl iodonium, an NADPH oxidase inhibitor, blocked in parallel astrocyte generation of reactive oxygen intermediates and expression of RA410 message [17].
• The iodonium compounds diphenyleneiodonium (DPI) and diphenyliodonium (IDP) are well-known phagocyte NAD(P)H oxidase inhibitors [14].
• This activity was suppressed by inhibitors of plasma membrane redox systems such as diphenylene iodonium, p-chloromercuribenzenesulfonic acid, and capsaicin, but was resistant to inhibition by resiniferatoxin and rotenone [18].
• However in a cell-free system, AA could trigger a redox signal via mechanisms that were profoundly disrupted by diphenylene iodonium, a flavoprotein inhibitor [19].
• Two components of the NADPH oxidase system, (1) a flavoprotein of 45 kDa which binds diphenylene iodonium (a compound described as a specific inhibitor of the leukocyte NADPH oxidase), and (2) a low-potential cytochrome b, are present in fibroblast membranes [20].

Associations of iodanium with other chemical compounds

• The NADPH inhibitor diphenylene iodonium and the superoxide dismutase mimetic manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) virtually abolished cytochalasin D-inhibitable actin monomer incorporation at the fast-growing barbed ends of filaments [21].
• Phorbol 12-myristate 13-acetate, guanosine 5'-3-O- (thio)triphosphate (GTP gamma S), or FMLP stimulated a similar diphenylene iodonium-sensitive diaphorase activity pattern in neutrophils and in differentiated parent PLB-985 cells [22].
• This increase in H2O2 was inhibited by extracellular catalase, diphenylene iodonium, an inhibitor of the NADH/NADPH oxidase, and the AT1 receptor blocker losartan [23].
• In-vitro incubation of platelets with angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase [24].
• Furthermore, the presence of E2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity [25].

Gene context of iodanium

• Activation of STATs by platelet-derived growth factor (PDGF) is significantly inhibited by N-acetyl-L-cysteine and diphenylene iodonium, indicating that ROS production contributes to STAT activation in response to PDGF [26].
• Moreover, the NADPH oxidase inhibitors apocynin and diphenylene iodonium were protective against IFN-gamma/LPS cytotoxicity only at concentrations that suppressed nitric oxide production [27].
• Stimulation of the cells with glutamate (100 mM) induced apoptotic cell death and increase in the level of ROS, and these effects of glutamate were significantly suppressed by the inhibitors of the NADPH oxidase, diphenylene iodonium, apocynin, and neopterine [28].
• Diphenylene iodonium inhibits the induction of erythropoietin and other mammalian genes by hypoxia. Implications for the mechanism of oxygen sensing [4].
• Diphenylene iodonium, a flavoenzyme inhibitor, blocked the effect of LPS on DJ-1/5.8 expression [29].

Analytical, diagnostic and therapeutic context of iodanium

• The 45 kDa diphenylene iodonium-binding flavoprotein of the human neutrophil superoxide-generating oxidase has been purified by affinity chromatography [30].
• Immobilization of aryl and alkynyl groups onto glassy carbon surfaces by electrochemical reduction of iodonium salts [31].
• A Cypridina luciferin analog-dependent chemiluminescent assay demonstrated that dolphin neutrophils generate superoxide by the addition of PMA, and that its superoxide-forming activity is completely suppressed by diphenylene iodonium, a specific inhibitor of NADPH oxidase [32].
• Pretreatment of the cell cultures with the NAD(P)H oxidase inhibitors diphenylene iodonium (2 and 10 microM) and quinacrine (1 and 5 mM) prevented the generation of H(2)O(2) under copper stress for 90% [33].

References