Ethylene from 2-keto-4-thiomethyl butyric acid: The Haber-Weiss reaction

Diguiseppi, James; Fridovich, Irwin

doi:10.1016/0003-9861(80)90114-9

Cited by 86 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar oxygen dependence was observed for demeclocycline (data not shown). The observed protection by 1 mM DTPA suggests that iron contaminants commonly found in the incubation buffers (10) H202 is generated by O2-dismutation. Photolytic deamination is the first step in the photodegradation of UVAilluminated tetracyclines (9,25).…”

Section: Resultsmentioning

confidence: 94%

“…The toxicity of oxygen for microorganisms has been variously attributed to superoxide (11), hydrogen peroxide (35), and the hydroxyl radical (10,13,35,36). The most reactive species, the hydroxyl radical, is formed in reactions involving O2, H202, and chelated iron (10,28 phototoxicity of tetracyclines. Urea, an ineffective hydroxyl radical scavenger, provided little protection when E. coli B was exposed to photoilluminated doxycycline and tetracycline ( Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B

Martin¹,

Colina²,

Logsdon³

1987

J Bacteriol

View full text Add to dashboard Cite

Photoillumination of tetracycline derivatives with low-intensity (320-to 400-nm) light and visible light generated superoxide, observed as the reduction of ferricytochrome c. The rate of reduction was dependent on the tetracycline concentration and on the derivative being examined, with doxycycline 2 demeclocycline > tetracycline > oxytetracycline. Tetracycline-mediated cytochrome c reduction was oxygen dependent and inhibited up to 70% by superoxide dismutase. Illuminated tetracyclines were lethal to Escherichia coli B incubated in a glucose minimal medium containing chloramphenicol. This lethality was light dependent, oxygen dependent, and dependent on the concentration of tetracycline. Kill rates also varied according to the derivative under study, with doxycycline . demeclocycline > tetracycline > oxytetracycline. The addition of superoxide dismutase and catalase to the incubation medium partialy protected E. coi B against the light-dependent lethality. Preinduction of intracellular superoxide dismutase and catalase substantially protected E. coli B against the phototoxicity of tetracyclines. Iron EDTA augmented the phototoxicity of tetracyclines, while diethylenetriaminepentaacetic acid protected against their lethality. Hydroxyl radical scavengers also conferred protection against tetracycline phototoxicity. The extent of protection was in order of the in vitro reactivity of the scavengers with the hydroxyl radical. These results indicate that superoxide, hydrogen peroxide, and the hydroxyl radical are generated by illuminated tetracyclines and are molecular agents of tetracycline phototoxicity in E. coli B.The tetracyclines are a group of antibiotics that are widely used to treat infections by both gram-positive and gramnegative bacteria. They inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit (7). Associated with the therapeutic use of tetracyclines are UVA (see below)-dependent side effects that include sunburn (14), papular eruptions (14, 15), and onchylosis (12). In addition, exposure to tetracyclines during UVA illumination lyses erythrocytes (5, 31), inhibits fibroblast growth (4), damages monocytes (24), and inactivates plant (30) and animal (32) viruses. The intracellular and intraviral targets for tetracycline photodamage are numerous: cytoplasmic membranes are ruptured in erythrocytes (5), tetracycline photoadducts are formed with ribosomal proteins in Escherichia coli (16), and single-strand breaks occur in bacteriophage 4X174 DNA (33). The molecular mechanisms underlying tetracycline photodamage in vivo are unknown. However, the phototoxicity is oxygen dependent, and the manifestations of tetracycline phototoxicity resemble cellular damage caused by oxygen radicals (11,13,(20)(21)(22)27). We have examined the involvement of oxygen radicals in tetracycline phototoxicity by demonstrating tetracycline-mediated oxygen radical generation in vitro and by characterizing the response of E. coli B to tetracycline phototoxicity in vivo. Bacterial cells are much more susceptible ...

show abstract

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B

Martin¹,

Colina²,

Logsdon³

1987

J Bacteriol

View full text Add to dashboard Cite

show abstract

“…Having confirmed the ability ofthe various proteases to cleave the two iron-binding proteins, the ability of the protease-treated diferrictransferrin and diferriclactoferrin complexes to function as a hydroxyl radical catalyst was examined. The oxidation of hypoxanthine by xanthine oxidase generates *°-and H202 but not hydroxyl radical (52,53). Thus, detection ofhydroxyl radical production by this reaction in the presence of an iron chelate is an indication ofthe ability ofthat chelate to function as a hydroxyl radical catalyst.…”

Section: Resultsmentioning

confidence: 99%

Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation.

Britigan

Edeker

1991

J. Clin. Invest.

View full text Add to dashboard Cite

In vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (7O-) and hydrogen peroxide (H202). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/ or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCI were added to a hypoxanthine/xanthine oxidase *02-/H202 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastasetreated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2-or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCI treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCI if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOC. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury. (J. Clin. Invest. 1991.

show abstract

“…Hypoxanthine (7) and ethylene production from a-keto-'y-methiolbutyric acid (KMB) (20,21). Although none of these reactions appears to be entirely specific (16,22), when the reactants are H202, superoxide and Fe(EDTA), the evidence is strongly in support of the hydroxyl radical being the reactive species (7,16 Myeloperoxidase was purified from human neutrophil granules (24).…”

Section: Introductionmentioning

confidence: 99%

“…When neutrophils were present, the solutions were centrifuged for 10 min at 2,000 g before the heating step. Hydroxyl radicals were also detected either by gas chromatographic measurement of ethylene production from KMB (5 mM) (20,26) or fluorimetric measurement (at pH 12) (excitation 300 nm, emission 410 nm) of hydroxylation products from benzoate (10 mM) (7). With both methods, the reaction with the xanthine oxidase system (in 1 ml total volume) was terminated after 30 min by adding 5O tg catalase.…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils.

Winterbourn¹

1986

J. Clin. Invest.

108

View full text Add to dashboard Cite

Hydroxyl radicals have been generated from hydrogen peroxide and superoxide (produced with xanthine oxidase), and an iron (EDTA) catalyst, and detected with deoxyribose, or in some cases with benzoate or a-keto-'y-methiolbutyric acid. Purified myeloperoxidase, and neutrophils stimulated with fMet-Leu-Phe and cytochalasin B, strongly inhibited this hydroxyl radical production in a concentration-dependent manner. Supernatants from stimulated cells also inhibited, and inhibition by cells or supernatant was prevented by azide. There was much less inhibition by myeloperoxidase-deficient neutrophils. Inhibition thus was due to myeloperoxidase released by the cells. With neutrophils stimulated with phorbol myristate acetate, which release very little myeloperoxidase, hydroxyl radical production was enhanced due to the additional superoxide produced by the cells. It is concluded that under conditions where neutrophils release myeloperoxidase as well as superoxide and hydrogen peroxide, breakdown of hydrogen peroxide by myeloperoxidase would make conditions unfavorable for hydroxyl radical production.

show abstract

Ethylene from 2-keto-4-thiomethyl butyric acid: The Haber-Weiss reaction

Cited by 86 publications

References 41 publications

Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B

Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B

Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation.

Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils.

Contact Info

Product

Resources

About