Gliotoxin inactivates alcohol dehydrogenase by either covalent modification or free radical damage mediated by redox cycling

Waring, Paul; Sjaarda, Allan; Lin, Qing H.

doi:10.1016/0006-2952(95)00039-3

Cited by 68 publications

(57 citation statements)

References 20 publications

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“…For some proteins, the cysteine residues that form mixed disulphide bonds with ETPs have been identified. For instance, gliotoxin forms a 1 : 1 covalent complex with alcohol dehydrogenase via cysteine residue 281 or 282 (Waring et al, 1995b). Gliotoxin catalyses formation of an internal disulphide bond between the physically close cysteines 282 and 73 in creatine kinase, which can be reversed by reducing agents (Hurne et al, 2000).…”

Section: Mechanisms Of Toxicitymentioning

confidence: 99%

The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis

2005

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Section: Mechanisms Of Toxicitymentioning

confidence: 99%

The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis

2005

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“…In addition, the rho kinase inhibitor Y27632, in that it has activity in a number of rather different disorders, such as hypertension, Alzheimer disease, bronchial asthma, and coronary heart disease, is likely to affect several signaling pathways (54)(55)(56)(57). Finally, gliotoxin is a known inducer of cellular apoptosis and can cause free radical damage (58,59). In contrast to these moreor-less nonspecific NF-κB inhibitors, the previously studied p65 antisense phosphorothioate ODN NF-κB inhibitor is as specific for NF-κB as the NF-κB decoy ODNs studied here (16).…”

Section: Figurementioning

confidence: 99%

Treatment of murine Th1- and Th2-mediated inflammatory bowel disease with NF- B decoy oligonucleotides

Fichtner‐Feigl

Fuss²,

Preiß³

et al. 2005

Journal of Clinical Investigation

159

116

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The Th1 and Th2 T cell responses that underlie inflammatory bowel diseases (IBDs) are likely to depend on NF-κB transcriptional activity. We explored this possibility in studies in which we determined the capacity of NF-κB decoy oligodeoxynucleotides (decoy ODNs) to treat various murine models of IBD. In initial studies, we showed that i.r. (intrarectal) or i.p. administration of decoy ODNs encapsulated in a viral envelope prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, as assessed by clinical course and effect on Th1 cytokine production. In further studies, we showed that NF-κB decoy ODNs were also an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/IL-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-κB decoy ODNs did not inhibit NF-κB in extraintestinal organs and resulted in CD4 + T cell apoptosis, suggesting that such treatment is highly focused and durable. Finally, we showed that NF-κB decoy ODNs also prevented and treated oxazolone-colitis and thus affect a Th2-mediated inflammatory process. In each case, decoy administration led to inflammation-clearing effects, suggesting a therapeutic potency applicable to human IBD.

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“…This structural feature of gliotoxin plays a highly significant role in mediating the virulence of A. fumigatus [3,4]. Gliotoxin is not immunogenic, and its toxicity in mammalian cells is generally enabled by direct inactivation of essential protein thiols, inhibition of NADPH oxidase assembly, in addition to promotion of redox cycling which leads to hydrogen peroxide formation [1,[5][6][7]. Sporidesmin A (Fig.…”

Section: Introductionmentioning

confidence: 99%

Single-pot derivatisation strategy for enhanced gliotoxin detection by HPLC and MALDI-ToF mass spectrometry

et al. 2011

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Gliotoxin is produced by non-ribosomal peptide synthesis and secreted from certain fungi, including Aspergillus fumigatus. It is an epipolythiodioxopiperazine that contains an intact disulphide bridge and is the focus of intense research as a consequence of its negative immunomodulatory properties. Gliotoxin detection is generally enabled by reversed-phase-high-performance liquid chromatography (RP-HPLC), with absorbance detection (220-280 nm), or liquid chromatography-mass spectrometry, yet detection is not readily achievable by matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry (MALDI-ToF MS). We have developed a single-pot derivatisation strategy which uses sodium borohydride-mediated reduction of gliotoxin followed by immediate alkylation of exposed thiols by 5′-iodoacetamidofluorescein to yield a stable product, diacetamidofluorescein-gliotoxin (GT-(AF) 2 ), of molecular mass 1103.931 Da ((M+H)+). This product is readily detectable by RP-HPLC and exhibits a 6.8-fold increase in molar absorptivity compared with gliotoxin, which results in a higher sensitivity of detection (40 ng; 125 pmoL). GT-(AF) 2 also fluoresces (excitation/emission, 492:518 nm). Unlike free gliotoxin, the product (>800 fmol) is detectable by MALDI-ToF MS. Sporidesmin A can also be detected by RP-HPLC and MALDI-ToF MS (>530 fmol) using this strategy. We also demonstrate that the strategy facilitates detection of gliotoxin (mean± SD = 3.55 ± 0.07 μg 100 μL −1 ; n = 2) produced by A. fumigatus, without the requirement for organic extraction of culture supernatants and associated solvent removal. GT-(AF) 2 is also detectable (150 ng; 460 pmol) by thinlayer chromatography.

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Gliotoxin inactivates alcohol dehydrogenase by either covalent modification or free radical damage mediated by redox cycling

Cited by 68 publications

References 20 publications

The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis

The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis

Treatment of murine Th1- and Th2-mediated inflammatory bowel disease with NF- B decoy oligonucleotides

Single-pot derivatisation strategy for enhanced gliotoxin detection by HPLC and MALDI-ToF mass spectrometry

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