Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Casentini-Borocz, D; Bringman, Timothy S.

doi:10.1128/aac.34.5.875

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…14 Accordingly, 5 mM H 2 O 2 , a signaling and growth stimulatory 17 dose, is added To further assess the impact of low-dose COS on Cblmediated cytotoxicity, COS is generated by GO treatment (10 ng ml À1 , 0.0026 U ml À1 ). GO, a high molecular weight protein, generates H 2 O 2 when it reacts with glucose, 18,19 which in turn produces superoxide anion (O 2 À ), which is converted by dismutases (Cu/ZnSOD to MnSOD and FeSOD) into H 2 O 2 . 20 As determined in preliminary studies, a dose of GO (10 ng ml À1 , 0.0026 U ml À1 ) causes an approximately twofold increase in intracellular levels of ROS and gives more consistent oxidative insult than does H 2 O 2 alone.…”

Section: Resultsmentioning

confidence: 99%

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Maiti

2009

Pharmacogenomics J

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Drug resistance in cancer cells involves complex molecular mechanisms and ovarian carcinoma cells become resistant to chlorambucil (Cbl) after continuous treatment. This drug-and ionizing radiation-resistant cells have lower level of endogenous ROS (reactive oxygen species) compared with sensitive cells. Elevation of the cellular ROS level by exogenous ROS generation increases the sensitivity of Cbl to resistant cells. In contrast, antioxidants prevent the sensitization of resistant cells to Cbl by H 2 O 2 , COS (chronic oxidative stress) or NOO À . The molecular mechanism of drug sensitivity with COS has been investigated by microarray gene expressions followed by gene network analysis and it reveals that a cdc42/rac1 guanine exchange factor, ARHGEF6, with p53 and DNA-Pkc (PRKDC) is central to induce apoptosis in Cbl cos (Cbl with COS) cells. mRNA and protein levels of major gene network pathway differ significantly in Cbl cos cells than in Cbltreated cells. Moreover, DNA-PKc physically interacts with ARHGEF6 and p53 mostly in the nucleus of Cbl-treated cells, whereas in Cbl cos -treated cells, its interactions are mostly in the cytoplasm. These results suggest that low doses of Cbl and very low doses of COS together kill Cbl-resistant ovarian carcinoma cells and ARHGEF6 signaling may have an instrumental role in induction of apoptosis in Cbl cos cells.

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Section: Resultsmentioning

confidence: 99%

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Maiti

2009

Pharmacogenomics J

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“…In the presence of an enzymatic H202-generating system and chloride ions, recMPO effectively displayed antimicrobial activity. Given the availability of an abundant source of enzymatically and biologically active recMPO, it is now worthwhile to evaluate the effective use of this enzyme as a preventive and/or curative agent against various infectious agents (Wright and Nelson, 1985;Rojas-Espinosa, 1989;Humphreys et al, 1989;Casentini-Borocz and Bringman, 1990).…”

Section: Discussionmentioning

confidence: 99%

Structural and biological properties of human recombinant myeloperoxidase produced by Chinese hamster ovary cell lines

Moguilevsky

Garcia‐Quintana

Jacquet

et al. 1991

European Journal of Biochemistry

124

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The cDNA encoding human myeloperoxidase carries three ATG codons in frame; 144,111 and 66 bp upstream from the proprotein DNA sequence. In order to determine the most efficient signal sequence, three cDNA modules starting at each of the ATG were cloned into an eucaryotic expression vector and stably expressed in Chinese hamster ovary cell lines. In all three cases, recombinant human myeloperoxidase (recMPO) was secreted into the culture medium of transfected cells, indicating that each of the signal peptides functions efficiently. One of the recombinant cell lines, which was amplified using methotrexate, overexpresses enzymatically active recMPO up to 6 pg * ml-' * day-'. The recombinant product was purified by a combination of ion-exchange and metalchelate chromatography, and characterized in terms of molecular mass, amino-terminal amino acid analysis, glycosylation, physicochemical properties and biological activity. The data show that recMPO is secreted essentially as a monomeric, heme-containing, single-chain precursor of 84 kDa which exhibits peroxidase activity. Aminoterminal analysis indicated that cleavage of the signal peptide occurs between amino acids 48 and 49. In addition, recMPO appeared to be glycosylated up to the last stage of sialylation, to an extent similar to that of the natural enzyme. Specific activity measurements as well as stability data, in various pH, temperature, ionic strength and reducing conditions, indicated that the recombinant single-chain enzyme behaves essentially in the same way as the natural two-chain molecule. Finally, recMPO was shown to exert potent cytotoxicity towards Escherichiu coli when provided with its physiological substrates, i. e. hydrogen peroxide and chloride ions.

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“…This system requires the combined presence of an oxidase, a peroxidase, and halide Fig. 1 to generate antiviral toxicity and has been previously used in enzyme ITs to kill tumor cells and various microorganisms (1,4,14,16,24). In the in vitro assays, presented here, GO and glucose produced H202, which then oxidized the added iodide salt in the presence of LPO or MPO.…”

Section: Discussionmentioning

confidence: 99%

“…The rationale for using these ITs was based on the observation of Klebanoff (16) that MPO or LPO, together with H202 and a halide, form a potent bactericidal system. Such ITs were also shown to be effective as antiinfectious agents in eliminating parasites, various bacteria (1), and yeasts such as Candida tropicalis (4).…”

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confidence: 99%

Virucidal effects of glucose oxidase and peroxidase or their protein conjugates on human immunodeficiency virus type 1

Yamaguchi¹,

Semmel²,

Stanislawski³

et al. 1993

Antimicrob Agents Chemother

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Glucose oxidase and peroxidase (lactoperoxidase or myeloperoxidase) are virucidal to human immunodeficiency virus type 1 (HIV-1) in the presence of sodium iodide, as assessed by the loss of viral replication in a syncytium-forming assay or by the inhibition of cytopathic effects on infected cells. In the presence of low concentrations of sodium iodide, five HlV-1 isolates were equally susceptible to this virucidal system at enzyme concentrations of a few milliunits. The loss ofviral replication was linearly related to the time of incubation in the enzyme solutions, with an inactivation rate of 1 log unit every 30 min. These enzymes and this halide were also cytotoxic to chronically infected, but not to uninfected, cultured CEM cells. Protein conijugates were prepared by using the enzymes and murine antibody 105.34, which recognized the V3 loop of H1V-i LAT isolate surface glycoprotein, or recombinant human CD4. The protein conjugates inactivated free virus at rates similar to those of the free enzymes and were more effective than antibody or recombinant CD4 alone. These in vitro findings demonstrate that the peroxidase-H202-halide system provides potent virucidal activity against HIV-1.

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Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Cited by 7 publications

References 21 publications

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

Structural and biological properties of human recombinant myeloperoxidase produced by Chinese hamster ovary cell lines

Virucidal effects of glucose oxidase and peroxidase or their protein conjugates on human immunodeficiency virus type 1

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