Almitrine prevents some hypoxia-induced metabolic injury in rat astrocytes.
During reperfusion of ischemic brain tissue, the production of reactive oxygen species initiates several modifications of the astroglial functional and ultrastructural integrity. During 24 h after ischemic treatment, modification of cellular superoxide free radical scavenging systems have been observed in primary culture of rat astroglial cell. Mitochondrial Mn superoxide dismutase activity (Mn-SOD) gradually decreases, whereas that of the cytosolic Cu,Zn form of the enzyme remains unaffected. We observed in parallel a significant decrease of glutamine synthetase (GS), an astrocyte specifically located enzyme. Addition of almitrine (dialylamine-4',6'-triazinyl 2')-1-(bis-parafluoro-benzydryl)-4-piperazine or dibucaine (a phospholipase A2 inhibitor) antagonizes the decrease of Mn-SOD activity, but does not affect modification of GS activity. Combined effects are observed by simultaneous addition of both drugs. Our data demonstrate that almitrine may increase the synthesis of some mitochondrial proteins, like Mn-SOD, and provide support for further study on the therapeutic potential of almitrine in ischemic astroglial cell injury.
Copin
J C
JC
Laboratoire de Neurobiologie Ontogenique, Centre de Neurochimie du CNRS, Strasbourg, France.
Ledig
M
M
Tholey
G
G
D015765:Almitrine / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D005609:Free Radicals; D005974:Glutamate-Ammonia Ligase / Q000187:drug effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000187:drug effects*
D005609:Free Radicals; D003513:Cycloheximide; D015765:Almitrine; D013482:Superoxide Dismutase; D005974:Glutamate-Ammonia Ligase; D003992:Dibucaine