Detail of "74149-38-5"

Reference

A Novel Redox Mechanism for the Glutathione-dependent Reversible Uptake of a Fungal Toxin in Cells

A Novel Redox Mechanism for the Glutathione-dependent Reversible Uptake of a Fungal Toxin in Cells. Bernardo, Paul H.; Brasch, Nicola; Chai, Christina L. L.; Waring, Paul ( Centre for the Study of Bioactive Molecules, Australian National University, Canberra 0200, Australia). Journal of Biological Chemistry, 278(47), 46549-46555 (English) 2003 American Society for Biochemistry and Molecular Biology. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The fungal metabolite gliotoxin is characterized by an internal disulfide bridge and can exist in either disulfide or dithiol forms. Gliotoxin and other members of the epipolythiodioxopiperazine class of toxins have immunosuppressive properties and have been implicated in human and animal mycotoxicoses. The bridged disulfide moiety is thought to be generally essential for biol. activity. Here we show that only the natural (oxidized) form of gliotoxin is actively concd. in a cell line in a glutathione-dependent manner. Intracellular levels of the toxin can be up to 1500-fold greater than the applied concn., and toxin in the cells exists almost exclusively in the reduced form. A simple model of toxin entry followed by redn. to the cell-impermeant dithiol explains active uptake, cell d. dependence of EC50 values and predicts a value for the max. concn. 35824-80-7 and 74149-38-5 which are cas registry numbers of chemicals are mentioned. of toxin at limiting cell d. in agreement with the expt. Oxidn. of the intracellular toxin results in rapid efflux from the cell that also occurs when glutathione levels fall following induction of apoptotic cell death by the toxin. This mechanism allows for minimal prodn. of the toxin while enabling maximal intracellular concn. and thus maximal efficacy of killing in a competitor organism initially present at low cell d. The toxin effluxes from the apoptotic cell exclusively in the oxidized form and can further enter and kill neighboring cells, thus acting in a pseudocatalytic way. .