Salen-manganese complexes: sophisticated tools for the analysis of intercellular ROS signaling pathways.

Salen-manganese complexes, such as EUK-8 and EUK-134 are known as catalase mimetics with superoxide dismutase (SOD) and peroxidase mimetic activity. Here we show that the concentration-dependent use of salen-manganese complexes within the appropriate time window and with parallel control of signaling parameters allows complex interactions during intercellular induction of apoptosis to be studied. At very low concentrations, salen-manganese complexes can abrogate consumption reactions between HOCl and hydrogen peroxide, as well as NO and hydrogen peroxide, and thus the major signaling pathways are enhanced. At higher concentrations of the compounds, all major signaling pathways are inhibited, thereby the catalase mimetic activity of the compounds affects both hydrogen peroxide and peroxynitrite. The ratio between available hydrogen peroxide and salen-manganese complexes defines whether reactive oxygen species (ROS) effects are inhibited or apoptosis is induced by the compounds. The SOD mimetic activity of salen-manganese complexes seems to be insufficient to interfere with intercellular ROS signaling.