Fig. 7

Concept explaining the effects of the zinc matrix metalloproteinase ZMP-2 on stress resistance in C. elegans as impaired by the transport of oxidized cholesterol adducts. Extracellular cholesterol can be exploited by the cells subsequent to its transport requiring VIT-6 and RME-2, in order to trigger the steroid signalling pathway. Extracellular ROS, however, can oxidize cholesterol or lipoproteins before their cellular uptake. Once inside the cell, oxidized cholesterol causes a cellular response which involves DAF-16 and consequently inhibits DAF-9 and DAF-12. Those effects are associated with reduced stress resistance and can be prevented either by reducing the uptake of oxidized cholesterol adducts or by ZMP-2, which is suggested to degrade such cytotoxic products