Disease relevance of Dithiothreitol

• Solution Structure and Backbone Dynamics of the Reduced Form and an Oxidized Form of E. coli Methionine Sulfoxide Reductase A (MsrA): Structural Insight of the MsrA Catalytic Cycle [1].
• Any toxicity produced by DTT alone was also antagonized by CGS-19755 [2].
• CONCLUSION: (1) Both DTT and cisplatin were able to induce apoptosis in esophageal cancer cell line Eca109; (2) P38 MAP kinase is essential for DTT- and cisplatin-induced apoptosis in Eca109 cells; (3) P38 activation may be the common signaling component relaying the multiple upstream signaling events to the downstream cell death program [3].

High impact information on Dithiothreitol

• The suppression in caspase-3-like activity in hepatocytes exposed to an NO donor was partially blocked by an inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one, (ODQ), while the incubation of these lysates in DTT almost completely restored caspase-3-like activity to the level of TNFalpha-treated controls [4].
• NO-dependent inhibition of T cell proliferation was associated with an inhibition of caspase activity and activation, and this effect was reversible by DTT [5].
• However, neither DTT nor GSH was able to reverse the effect of NO*. In contrast to SIN-1, DTT had no effect when added to the cis (extracellular) side of the chamber [6].
• In contrast, when intact PAEC or isolated total membranes derived from PAEC were treated with increasing concentrations (1 to 5 mM) of the disulfide-reducing agent dithiothreitol (DTT), but not oxidized DTT, NO synthase activity was increased by 20 to 85% [7].
• Complete protection from DTT inhibition of [3H]FNZ binding by FNZ (an agonist) or by Ro 15-1788 (an antagonist) suggests the presence of -SS- at, or very close to, the BZD recognition binding site [8].

Biological context of Dithiothreitol

• Endogenous SH compounds, which have similar chemical structures to DTT, would participate in nickel carcinogenesis through causing oxidative DNA damage [9].
• In combination with 1 mM dithiothreitol (DTT), the reductive cofactor for the microsomal enzyme vitamin K epoxide reductase, vitamin K suppressed lipid peroxidation with a concentration that blocked the maximal response by 50% (IC50) of ca. 0.2 microM [10].
• The rates for DTT, cisplatin, and DTT plus cisplatin-induced apoptosis were 16.8%, 17.1%, and 21.4%, respectively [3].
• This treatment also resulted in a reduction of binding activity with an IC50 of 20 mM for DTT [11].
• Addition of dithiothreitol (DTT) prevented the drop in membrane potential and completely prevented cell killing by allyl alcohol [12].

Anatomical context of Dithiothreitol

• It has been shown previously that the thioredoxin system (thioredoxin + thioredoxin reductase + NADPH) may replace dithiothreitol (DTT) as a cofactor for vitamin KO and K reductase in salt-washed detergent-solubilized bovine liver microsomes [13].
• Photoaffinity labeling experiments with [3H]FNZ revealed a clear-cut band of 50 kDa in native and alkylated membranes but an extremely weak label in 5 mM DTT/IAA-treated membranes [8].
• A biphasic response to DTT was obtained with BNF microsomes; inhibition of N-demethylation was seen only at low concentrations (0.1 mM) and a return to control values occurred at higher concentrations [14].
• AFM inhibition was enhanced by preincubation of barley organelle extract in the presence of DTT [15].
• Dithiothreitol (DTT), a sulfhydryl (SH) compound, failed to protect against the suppression of lymphocyte function by anthralin [16].

Associations of Dithiothreitol with other chemical compounds

• These results suggest that Ni(II) and DTT form a reactive species, which may be responsible for causing guanine-specific DNA damage [9].
• DNA damage induced by Ni(II) plus DTT was observed only when the DNA was treated with piperidine, suggesting that Ni(II) plus DTT caused only base damage [9].
• Sodium azide, a potent and relatively specific scavenger of (1)O(2), inhibited DNA damage by Ni(II) in the presence of DTT, whereas the sequence specificity of DNA damage was different from that obtained by (1)O(2) generating agent [9].
• The inactivation could be attenuated by antioxidants such as vitamin E, reduced glutathione, and menadione and also by a K vitamin in combination with DTT, but not by superoxide dismutase and catalase [10].
• Investigation into the mechanism of this inactivation showed that quinone-like compounds were reduced by DTT establishing a reactive oxygen generating redox cycle the products of which (likely H(2)O(2)) inactivated the enzyme [17].

Gene context of Dithiothreitol

• Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ(2) [18].
• Neither GSH nor DTT could restore lost ALDH activity after exposure of the enzyme to MeDTC sulfone [19].
• The concentration of DTT required to obtain maximal enzyme activity may be as much as 485 times greater than the corresponding concentration of reduced thioredoxin that gives the same enzyme activity [20].
• Activity of enolase inhibited by both acrylamide and DTT could not be restored to pre-inhibition rates following dialysis indicating that an irreversible interaction between acrylamide and enolase had taken place [21].
• NO-induced loss of the catalytic activity of PKC-zeta was restored by incubation with the disulfide reducing agent dithiothreitol (DTT) as well as by purified thioredoxin or thioredoxin reductase [22].

Analytical, diagnostic and therapeutic context of Dithiothreitol

• ELISA estimations of rheumatoid factor IgM, IgA, and IgG in sera from RA patients with high disease activity. DTT treatment studies [23].

References