I have been using HDAC inhibitors (HDACis) to study their effects on NETosis and apoptosis. I am using human neutrophils.
I specifically use belinostat and panobinostat as they inhibit most of HDACs.
My results show increased levels of reactive oxygen species (ROS) when I treat neutrophils with increasing concentrations of belinostat and panobinostat.
My questions is: How do HDAC inhibitors (especially belinostat and panobinostat) promote ROS levels? Like do HDACis activate any kinases or molecules that would promote ROS levels?
This would be very helpful as I am searching for a way to inhibit HDACis-induced ROS levels.
Vorinostat up-regulates thioredoxin-binding protein-2 (TBP-2), which inhibits redox protein thioredoxin, and this subsequently leads to the accumulation of ROS. This mechanism seems to be mediated through inhibition of HDAC10, so it can also explain accumulation of ROS in cells treated with belinostat and panobinostat.
Thank you Roman Mezencev this is very helpful.
I wish if there was an inhibitor for TBP-2 so I can easily check the ROS levels. I guess western blots are the only way.
Thank you again
You are welcome. There is a possibility to knock-down TBP-2 with siRNA and check whether treatment with HDAC inhibitors still increases ROS in these cells.