Disease relevance of Dithiothreitol

• Linear simian virus 40 (SV40) chromosomes were prepared by Eco R1 nuclease cleavage of the circular SV40 chromosomes released from virions with dithiothreitol at pH 9,8 [1].
• METHODS: Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn's disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21) [2].
• Plasma samples from normal subjects, children with haemolytic uraemic syndrome (HUS), and adults with vasculitis and vWF prepared from endothelium were treated with DTT before vWF assay. vWF in HUS and vasculitis resembled the endothelial form in being resistant to reduction [3].
• Also, we show that, contrary to earlier results, ompL null mutations alone do not result in partial DTT sensitivity or partial motility, nor do they appreciably affect bacterial growth rates or block propagation of the male-specific bacteriophage M13 [4].
• Using influenza hemagglutinin (HA0) and vesicular stomatitis virus G protein as model proteins, we have analyzed the effects of dithiothreitol (DTT) on conformational maturation and transport of glycoproteins in the secretory pathway of living cells [5].

Psychiatry related information on Dithiothreitol

• The reaction times for the complete conversion of DHAA to AA at room temperatures were 150, 120, 90 and 75 min for 1, 2, 4 and 8 mmol DTT per mmol of DHAA, respectively [6].
• The addition of the disulfide reducing agent dithiothreitol inhibited the cell-free conversion reaction with an IC50 of 2-2.5 mM [7].
• The effect of NaN(3) upon the response to serotonin, which was not blocked by either glutathione ethyl ester (GTEE) or dithiothreitol (DTT), was similar in platelets obtained from patients with Alzheimer's disease and from age- and gender-matched controls [8].

High impact information on Dithiothreitol

• Dithiothreitol, a thiol reductant, reversed the analgesia induced by cupric ion and antagonized analgesia induced by morphine [9].
• A marked dithiothreitol-induced increase in the monodeiodination by fetal sheep liver homogenates suggests that the characteristically low conversion in fetal tissues is related more to the status of sulfhydryl groups than to a deficiency of the monodeiodinating enzyme [10].
• This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol [11].
• Perturbation of the folding environment in intact cells with the reducing agent dithiothreitol or the trimming glucosidase inhibitor N-7-oxadecyl-deoxynojirimycin prolongs the presence of mAb-reactive K(b) heavy chains [12].
• It could not be eluted by high-ionic-strength saline, EDTA, dithiothreitol, or either polar or nonpolar detergents, but was released into solution when isolated glomerular basement membrane was digested by highly purified bacterial collagenase [13].

Chemical compound and disease context of Dithiothreitol

• Although ISF shares several biochemical properties with a murine sarcoma virus-transformed cell-derived sarcoma growth factor (e.g., acetic acid solubility and sensitivity to dithiothreitol), the two factors could be resolved by gel filtration on Bio-Gel P-60 [14].
• We demonstrate that this allosterically modulated regulatory protein is sensitive to HgCl2 concentrations of 1.0 +/- 0.3 x 10(-8) M in the presence of 1.0 x 10(-3) M dithiothreitol for half-maximal induction of transcription of the mer promoter by Escherichia coli RNA polymerase in vitro [15].
• In particular, the BPTI produced by E. coli had three disulfide bonds that appeared to be identical to those found in native BPTI, as assayed by sensitivity to iodoacetate, dithiothreitol, and urea [16].
• The activity was highly dependent on intact disulfides, because the bactericidal effect on Escherichia coli and the cytolytic effect on human 3B6 lymphocytes was inhibited when NK-lysin was treated with dithiothreitol prior to incubation with the cells [17].
• The enzyme requires anaerobic activation by two E. coli fractions with S-adenosylmethionine, NADPH, dithiothreitol, and KCl [18].

Biological context of Dithiothreitol

• In these, but not in NR1-NR2A, the DTT effect was rendered insensitive to reoxidation by alkylation [19].
• We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins [20].
• (EMBO J., 19, 5980-5988, 2000) reported that null mutations in the ompL gene of E.coli fully suppress all phenotypes associated with dsbA mutants, i.e. sensitivity to the reducing agent dithiothreitol (DTT) and the antibiotic benzylpenicillin, lack of motility, reduced alkaline phosphatase activity and mucoidy [4].
• Active site mutations in yeast protein disulfide isomerase cause dithiothreitol sensitivity and a reduced rate of protein folding in the endoplasmic reticulum [21].
• Hemagglutination assays showed that the lectin was inactivated by horse serum and by chick embryo extract but not by L-15 salt solution at 4 degrees C. Incubation in L-15 solution at 37 degrees C with or without 2 mM dithiothreitol resulted in inactivation in 2--3 h [22].

Anatomical context of Dithiothreitol

• Only the sulfhydryl compounds, cysteine, dithiothreitol, and mercaptoethanol protected erythrocytes from FP [23].
• Effect of dithiothreitol on plasma membrane intramembranous particle topography in BALB/c 3T3 and simian virus-transformed 3T3 cells and plasma membrane vesicles [24].
• In contrast, PTU did not affect the composition of labeled iodothyronines in the placenta effluents, despite the fact that the addition of PTU significantly (P less than 0.001) inhibits the inner-ring deiodination of [125I]T3 in human or guinea pig placenta microsomes in the presence of low (0.25 mM) concentrations of dithiothreitol [25].
• Viable suspensions of human colonic mucosal lymphoid cells have been prepared by sequential treatment of tissue with dithiothreitol, EDTA in calcium- and magnesium-free salt solutions, and purified collagenase [26].
• Cultured human endothelial cells were labeled with (3H)leucine, and the radioactive Factor VIII antigen present in the postculture medium was isolated by double anitbody immunoprecipitation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction with dithiothreitol [27].

Associations of Dithiothreitol with other chemical compounds

• RESULTS: One hundred percent reactivation of ATPase following inhibition in vivo by omeprazole or its enantiomers was seen with dithiothreitol and 89% with glutathione [28].
• However, its effects on T lymphocyte proliferation can be reversed by reducing agents like 2-mercaptoethanol or dithiothreitol, suggesting that oxidative substances are contained in mucosal supernatants [29].
• Because Tg has multiple disulfides, as well as glycans, we tested a brief exposure of live thyrocytes to dithiothreitol, which resulted in quantitative aggregation of nascent Tg, as analyzed by SDS-PAGE of cells lysed without further reduction [30].
• Therefore, we believe that these four proteins also effec the temperature-dependent gelation and aggregation of crude sucrose extracts pulmonary macrophages containing Mg2-ATP and dithiothreitol [31].
• This defect could be rescued by the addition of either oxidized DTT or cystine or by multicopy expression of dsbA, a known periplasmic disulfide oxidase [32].

Gene context of Dithiothreitol

• The activity of the CM was eliminated by boiling and by treatment with trypsin, pepsin, or dithiothreitol and was additive with saturating concentrations of acidic fibroblast growth factor, epidermal growth factor, and insulin [33].
• In cells expressing the NR1-NR2B, -NR2C, and -NR2D channels DTT elicited only a slowly developing, persistent potentiation and increased the deactivation time course [19].
• Null mutations in dsbC were obtained using a screen for dithiothreitol (DTT)-sensitive mutants and were shown to result in the accumulation of reduced forms of a variety of disulfide bond-containing periplasmic proteins [32].
• APR-mediated APS reduction is dependent on dithiothreitol, has a pH optimum of 8.5, is stimulated by high ionic strength, and is sensitive to inactivation by 5'-adenosinemonophosphate (5'-AMP) [34].
• Thus, diamide treatment of nuclear extracts strongly reduces the binding of NFI proteins, and the addition of higher concentrations of dithiothreitol to nuclear extracts from TG-treated cells restores NFI-DNA binding to levels in extracts from untreated cells [35].

Analytical, diagnostic and therapeutic context of Dithiothreitol

• Examination of dithiothreitol reduced samples before and after treatment with Reptilase or thrombin revealed that the Aalpha- and Bbeta-chains could release the A and B peptides, respectively [36].
• DTT modification of the ELISA assay may be useful as a marker of disease severity in conditions associated with endothelial cell damage [3].
• When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and sigma for albumin but not fibrinogen decreased [20].
• Since dithiothreitol-treated eggs did not elevate a fertilization membrane, scanning electron microscopy could be used to directly observe modifications in the egg plasma membrane after fertilization [37].
• Because in quantitative bioassays fertilization was found to be inhibited by treatment of eggs with 5 mM dithiothreitol, we undertook more direct studies of the effect of reduction on properties of the receptor [38].