Low dose (-)deprenyl is cytoprotective: it maintains mitochondrial membrane potential and eliminates oxygen radicals.
Hypoxia leads to a collapse in mitochondrial transmembrane potential (Deltapsi(M)), a fall in the ATP/ADP ratio, and finally cell death. Since (-)deprenyl directly modulates Deltapsi(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. Deltapsi(M) shifted to lower values following hypoxia/re-oxygenation and all cells had decreased and uniform Deltapsi(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 Deltapsi(M) shift caused by oxygen deprivation was reversed and the peroxy radical levels decreased except for at 10(-3) M.
Simon
L
L
National Institute of Psychiatry and Neurology, National Stroke Center, Department of Vascular Neurology, Semmelweis University, Budapest H-1021 Hungary. simla@freemail.hu
Szilágyi
G
G
Bori
Z
Z
Telek
G
G
Magyar
K
K
Nagy
Z
Z
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012642:Selegiline / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D012642:Selegiline; D010100:Oxygen