Assessment of Structural Features of the Pseudomonas Siderophore Pyochelin Required for Its Ability to Promote Oxidant-Mediated Endothelial Cell Injury

DeWitte, Jon J.; Cox, Charles D.; Rasmussen, George T.; Britigan, Bradley E.

doi:10.1006/abbi.2001.2517

Cited by 16 publications

(12 citation statements)

References 25 publications

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“…In the absence of heme, the inclusion of coprogen into the reaction mixtures did not generate LDL oxidation, and did not result in HO-1 induction either. This means that, similar to the bacterial desferrioxamine B, iron ions buried in fungal hexadentate trihydroxamates are not "redox-active" unlike the tridentate P. aeruginosa siderophore pyochelin [26,27]. Two of the tested four siderophores, coprogen, and ferrichrome -both produced by cheese-ripening Penicillium spp.…”

Section: Discussionmentioning

confidence: 99%

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Fungal siderophores function as protective agents of LDL oxidation and are promising anti‐atherosclerotic metabolites in functional food

Pócsi

Jeney

Kertai

et al. 2008

Molecular Nutrition Food Res

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Iron-mediated oxidation of low-density lipoprotein has been implicated in the pathogenesis of vascular disorders such as atherosclerosis. The present investigations were performed to test whether hydrophobic fungal siderophores -hexadentate trihydroxamates desferricoprogen, desferrichrome, desferrirubin, and desferrichrysin -might suppress heme-catalyzed LDL oxidation and the toxic effects of heme-treated LDL on vascular endothelium. Indeed, two of these -desferricoprogen and desferrichrome -markedly increased the resistance of LDL to heme-catalyzed oxidation. In similar doseresponse fashion, these siderophores also inhibited the generation of LDL products cytotoxic to human vascular endothelium. When iron-free fungal siderophores were added to LDL/heme oxidation reactions, the product failed to induce heme oxygenase-1, a surrogate marker for the noncytocidal effects of oxidized LDL (not in the case of desferrichrysin). Desferricoprogen also hindered the ironmediated peroxidation of lipids from human atherosclerotic soft plaques in vitro, and was taken up in the gastrointestinal tract of rat. The absorbed siderophore was accumulated in the liver and was secreted in its iron-complexed form in the feces and urine. The consumption of mold-ripened food products such as aged cheeses and the introduction of functional foods and food additives rich in fungal iron chelators in diets may lower the risk of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

“…Numerous other unicellular organisms also produce siderophores but many of these have little promise for clinical use. For example, a siderophore produced by Pseudomonas aeruginosa, pyochelin, does not suppress iron-mediated oxidation/reduction reactions and may even augment oxidant cell injuries [26,27].…”

Section: Introductionmentioning

confidence: 99%

Fungal siderophores function as protective agents of LDL oxidation and are promising anti‐atherosclerotic metabolites in functional food

Pócsi

Jeney

Kertai

et al. 2008

Molecular Nutrition Food Res

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“…Hydroxyl radical formation was determined by using a lumazine/xanthine oxidase system and spin trapping-electron paramagnetic resonance (EPR) spectrometry, as previously described (8). Transferrin fragments were generated by incubating equal volumes of holotransferrin (2 mg/ml in PBS), dithiothreitol (2.5 mM), and the preparation containing Arg-gingipains A and B (300 U/ml) for 2 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Cleavage of Human Transferrin by Porphyromonas gingivalis Gingipains Promotes Growth and Formation of Hydroxyl Radicals

et al. 2004

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Porphyromonas gingivalis, a gram-negative anaerobic bacterium associated with active lesions of chronic periodontitis, produces several proteinases which are presumably involved in host colonization, perturbation of the immune system, and tissue destruction. The aims of this study were to investigate the degradation of human transferrin by gingipain cysteine proteinases of P. gingivalis and to demonstrate the production of toxic hydroxyl radicals (HO ⅐ ) catalyzed by the iron-containing transferrin fragments generated or by release of iron itself. Analysis by polyacrylamide gel electrophoresis and Western immunoblotting showed that preparations of Arg-and Lys-gingipains of P. gingivalis cleave transferrin (iron-free and iron-saturated forms) into fragments of various sizes. Interestingly, gingival crevicular fluid samples from diseased periodontal sites but not samples from healthy periodontal sites contained fragments of transferrin. By using 55 Fe-transferrin, it was found that degradation by P. gingivalis gingipains resulted in the production of free iron, as well as iron bound to lower-molecular-mass fragments. Subsequent to the degradation of transferrin, bacterial cells assimilated intracellularly the radiolabeled iron. Growth of P. gingivalis ATCC 33277, but not growth of an Arg-gingipainand Lys-gingipain-deficient mutant, was possible in a chemically defined medium containing 30% ironsaturated transferrin as the only source of iron and peptides, suggesting that gingipains play a critical role in the acquisition of essential growth nutrients. Finally, the transferrin degradation products generated by Arg-gingipains A and B were capable of catalyzing the formation of HO ⅐ , as determined by a hypoxanthine/ xanthine oxidase system and spin trapping-electron paramagnetic resonance spectrometry. Our study indicates that P. gingivalis gingipains degrade human transferrin, providing sources of iron and peptides. The iron-containing transferrin fragments or the release of iron itself may contribute to tissue destruction by catalyzing the formation of toxic HO ⅐ .Periodontitis is a chronic inflammatory disorder of the periodontium initiated by an overgrowth of specific bacterial species and characterized by the destruction of tooth-supporting connective tissues, including the alveolar bone. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, has been implicated as a major etiological agent in the onset and progression of chronic periodontitis (33). Arg-and Lys-gingipain cysteine proteinases, which occur in multiple molecular forms due to proteolytic processing of the initially translated polypeptides, are the main endopeptidases produced by P. gingivalis (12,15,16). Two genes code for Arg-gingipains (rgpA and rgpB), and one gene codes for Lys-gingipain (kgp) (12,15,16). An increasing number of reports have stressed the potential roles of Arg-and Lys-gingipains of P. gingivalis in the pathogenesis of this disease, as they are able to degrade a variety of tissue and plasma proteins and have the potential...

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“…Due to its highly reactive and short-lived nature (4), HO· diffused only a negligible distance before encountering an oxidizable substrate (9). HO· must be generated in close proximity to a target to cause its decomposition.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Augmentation of Organotin Decomposition by Ferripyochelin: Formation of Hydroxyl Radical and Organotin-Pyochelin-Iron Ternary Complex

Sun

Zhong

2006

Appl Environ Microbiol

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Pyochelin (PCH), a kind of siderophore secreted by Pseudomonas aeruginosa, was recently found to have triphenyltin (TPT)-decomposing capacity. In this work, significant augmentation of TPT decomposition by ferripyochelin (FePCH), the chelating compound of PCH with iron, was demonstrated in Tris-HCl buffer (pH 8.0). The generation of hydroxyl radical (HO·) in the presence of FePCH was observed. Inhibition of HO· generation by adding catalase and HO· scavengers (methanol and dimethyl sulfoxide) decreased TPT decomposition, while an increase in HO· formation in the presence of H 2 O 2 enhanced its decomposition. Our findings indicated that HO· generated in the reaction system was responsible for the enhanced TPT decomposition by FePCH versus PCH. The existence of the TPT-pyochelin-iron ternary complex was demonstrated by electron spray ionization-mass spectrometry, tandem mass spectrometry, and 1 H nuclear magnetic resonance. On the basis of the above results, HO· produced in the presence of FePCH was deduced to be in close proximity to TPT and has more opportunity to attack the Sn-C bond, which resulted in the enhanced organotin decomposition. The information obtained may have considerable environmental significance.Triorganotin compounds, in particular triphenyltin (TPT), have been introduced into the aquatic environment in large quantities due to their extensive use as pesticides in agriculture and as antifouling agents in boat paints (11). As a highly toxic compound, TPT has caused harmful effects on a variety of nontarget organisms, such as mollusks and fish (2, 12), even at aqueous concentrations of a few nanograms per liter (2). Although organotins are banned in most developed countries, they are still being introduced into water and sediment around the world, causing an obvious health risk that has raised public interest in the removal of organotin in and from the environment (14). Microorganisms play a crucial role in organotin removal from the natural environment because of their surprising ability under evolution to degrade xenobiotics (26).Several strains have been isolated from the sediment or soil, and TPT degradation by these strains was investigated under pure culture conditions (13, 24). Although microbe-mediated dealkylation of organotin has been reported, information about details of the mechanism of microbial TPT degradation/ decomposition is still limited (13,14). Walts and Walsh (25) demonstrated that only a few kinds of organotins were substrates for bacterial organomercurial lyase. Most organotin compounds, such as tributyltin and triethyltin, were not substrates for lyase, and some even caused irreversible inhibition of enzymes. Inoue and coworkers (13, 14) have identified a kind of siderophore, pyoverdine (PVD), which was produced by Pseudomonas chlororaphis and was capable of decomposing triphenyltin and tributyltin. We recently showed that pyochelin (PCH), a siderophore secreted by Pseudomonas aeruginosa, could decompose triphenyltin, and its decomposition mechanism was proposed as che...

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Assessment of Structural Features of the Pseudomonas Siderophore Pyochelin Required for Its Ability to Promote Oxidant-Mediated Endothelial Cell Injury

Cited by 16 publications

References 25 publications

Fungal siderophores function as protective agents of LDL oxidation and are promising anti‐atherosclerotic metabolites in functional food

Fungal siderophores function as protective agents of LDL oxidation and are promising anti‐atherosclerotic metabolites in functional food

Cleavage of Human Transferrin by Porphyromonas gingivalis Gingipains Promotes Growth and Formation of Hydroxyl Radicals

Mechanism of Augmentation of Organotin Decomposition by Ferripyochelin: Formation of Hydroxyl Radical and Organotin-Pyochelin-Iron Ternary Complex

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