Low dose (−)deprenyl is cytoprotective: It maintains mitochondrial membrane potential and eliminates oxygen radicals

Hypoxia leads to a collapse in mitochondrial transmembrane potential (ΔψM), a fall in the ATP / ADP ratio, and finally cell death. Since (−)deprenyl directly modulates ΔψM and production of reactive oxygen species (ROS) by altering the respiratory function of mitochondria, we were interested in the dose-response relations of these effects. The changes in JC-1 red / green signal ratios {mitochondrial transmembrane potential}, and the changes in the cerium staining (intracellular ROS) in hypoxic and normoxic PC12 cell cultures were measured following 1 h of Argon hypoxia and 24 h of re-oxygenation in the absence and in the presence of various concentrations of (−)deprenyl. ΔψM shifted to lower values following hypoxia/re-oxygenation and all cells had decreased and uniform ΔψM levels. The amount of ROS increased. Following 24 h of treatment with various concentrations of (−)deprenyl during the re-oxygenation period, survival increased, the ΔψM shift caused by oxygen deprivation was reversed and the peroxy radical levels decreased except for at 10− 3 M.