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

• Published in: Life sciences (1973) 2005-12, Vol.78 (3), p.225-231
• Main Authors: Simon, L., Szilágyi, G., Bori, Z., Telek, G., Magyar, K., Nagy, Z.
• Format: Article
• Language: English
• Subjects: (−)Deprenyl; Animals; Cell Death - drug effects; Cell Hypoxia - physiology; Cerium; Cytoprotection - drug effects; Dose-Response Relationship, Drug; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Intracellular Membranes - physiology; JC-1; Membrane Potentials - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial transmembrane potential; Oxygen - metabolism; PC12 Cells; Rats; Reactive oxygen radicals (ROS); Reactive Oxygen Species - metabolism; Selegiline - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.04.078

Hypoxia leads to a collapse in mitochondrial transmembrane potential (Δ ψ M), a fall in the ATP / ADP ratio, and finally cell death. Since (−)deprenyl directly modulates Δ ψ M 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. Δ ψ M shifted to lower values following hypoxia/re-oxygenation and all cells had decreased and uniform Δ ψ 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 Δ ψ M shift caused by oxygen deprivation was reversed and the peroxy radical levels decreased except for at 10 − 3 M.