Rasagiline, a monoamine oxidase-B inhibitor, protects NGF-differentiated PC12 cells against oxygen-glucose deprivation.
In our in vitro model, rasagiline a selective irreversible monoamine oxidase-B (MAO-B) inhibitor, protected nerve growth factor (NGF)-differentiated PC12 cells from cell death under oxygen and glucose deprivation (OGD). The severity of the OGD insult, as expressed by cell death, was time-dependent. Exposure of the cells to OGD for 3 hr followed by 18 hr of reoxygenation caused about 30-40% cell death. Under these conditions, the neuroprotective effect of rasagiline was dose-dependent: rasagiline reducing OGD-induced cell death by 68% and 80% at 100 nM and 1 microM, respectively. The neuroprotective effect of rasagiline was also observed when added after the OGD insult (55% reduction in cell death). Under rasagiline treatment, there was a lesser decrease in ATP content in cultures exposed to OGD compared with that in untreated cultures. OGD followed by reoxygenation resulted in a several fold increase in PGE(2) release into the extracellular medium. Rasagiline (100 nM-1 microM) markedly inhibited OGD-induced PGE(2) release. Clorgyline, a monoamine oxidase-A (MAO-A) inhibitor, did not protect NGF-differentiated PC12 cells against OGD-induced cell death. As NGF-differentiated PC12 cells contain exclusively MAO type A, these data suggest that the neuroprotective effect of rasagiline under OGD conditions is independent of MAO inhibition.
Abu-Raya
S
S
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Blaugrund
E
E
Trembovler
V
V
Shilderman-Bloch
E
E
Shohami
E
E
Lazarovici
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; D007511:Ischemia; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; C031967:rasagiline; D000255:Adenosine Triphosphate; D008995:Monoamine Oxidase; D005947:Glucose; D015232:Dinoprostone