Opposing effects of polysulfides and thioredoxin on apoptosis through caspase persulfidation
Ilana Braunstein, Rotem Engelman, Ofer Yitzhaki, Tamar Ziv, Erwan Galardon, Moran Benhar
Abstract
We further found that under conditions of low TrxR activity, early cell exposure to polysulfides leads to enhanced persulfidation of initiator caspase-9 and decreases apoptosis. Notably, we show that the proenzymes procaspase-3 and -9 are basally persulfidated in resting (unstimulated) cells and become depersulfidated during their processing and activation. Inhibition of TrxR attenuated the depersulfidation and activation of caspase-9. Taken together, our results reveal that polysulfides target the caspase-9/3 cascade and thereby suppress cancer cell apoptosis, and highlight the role of Trx/TrxR-mediated depersulfidation in enabling caspase activation.
Topics & Concepts
ThioredoxinApoptosisChemistryCell biologyCaspaseCaspase 3BiochemistryBiologyProgrammed cell deathOxidative stressSulfur Compounds in BiologyRedox biology and oxidative stressAir Quality and Health Impacts