Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 277, Issue 35, Pages 31631-31638Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M201699200
Keywords
-
Categories
Ask authors/readers for more resources
Gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins, induces both apoptotic and necrotic cell death in a concentration-dependent manner. Whereas the specific trigger for apoptotic death caused by these toxins is unclear, the reactive disulfide bond in the ETP toxins is required for biological activity. Thus it is likely that it is the interaction of this disulfide moiety with macromolecules in cells that was responsible for activity of ETP toxins. Here we present evidence that necrosis induced by gliotoxin and a simple synthetic ETP toxin is largely because of an influx of extracellular calcium through a redox-sensitive calcium channel in the plasma membrane of murine thymocytes. The calcium rises are strongly dependent on the pH of the external medium and the presence of external calcium and are abrogated and/or reversed by the presence of dithiothreitol, cell impermeant glutathione, and the calcium channel blocker Ni2+. Comparisons with thapsigargin, which indirectly causes release of calcium from internal stores, indicates that ETP toxins do not provoke calcium rises by store depletion. A mechanism of oxidation by ETP toxins of cell surface thiol groups resulting in direct entry of calcium through a redox active channel in the plasma membrane is proposed. Necrotic but not apoptotic cell death was abrogated by inhibition of calcium entry.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available