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

Hypoxia leads to a collapse in mitochondrial transmembrane potential (Delta phi(M)), a fall in the ATP/ADP ratio, and finally cell death. Since (-)deprenyl directly modulates Delta phi(M) and production of reactive oxygen species (ROS) by altering the respiratory function of initochondria, we were interested in the dose-response relations of these effects. The changes in JC-I red/green signal ratios {mitochondrial transmembrane potential), and the changes in the cerium staining (intracellular ROS) in hypoxic and normoxic PC 12 cell cultures were measured following I h of Argon hypoxia and 24 h of re-oxygenation in the absence and in the presence of various concentrations of (-)deprenyl. Aom shifted to lower values following hypoxia/re-oxygenation and all cells had decreased and uniform Delta phi(M) levels. The amount of ROS increased. Following 24 h of treatment with various concentrations of (-)deprenyl during the re-oxygenation period, survival increased, the Aom shift caused by oxygen deprivation was reversed and the peroxy radical levels decreased except for at 10(-3) M. (c) 2005 Elsevier Inc. All rights reserved.