(-)Deprenyl-N-oxide, a (-)deprenyl metabolite, is cytoprotective after hypoxic injury in PC12 cells, or after transient brain ischemia in gerbils

Géza Szilágyi, László Simon, Edina Wappler, K. Magyar, Zoltán Nagy

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background and aims: (-)-Deprenyl (selegiline) possesses cyto-protective effect in a much lower concentration, than it is needed to inhibit MAO-B activity. In permanent MCA occlusion stroke model in rats, the infarct volume and the number of apoptotic neurons in the penumbra region were decreased by low concentration (-)deprenyl treatment. Augmented Bcl-2 protein expression was documented as the responsible factor of this effect. The stabilization of mitochondrial membrane and diminished ROS production are the further possible consequences of (-)deprenyl treatment. It is not clear however that (-)deprenyl, or its metabolites are the acting neuroprotective molecules in the hypoxic/ischemic conditions. We report here the possible cyto-protective effect of deprenyl-N-oxide (DNO), a recently synthesized (-)deprenyl metabolite. Methods: DNO in a very low dose (10- 5,- 8,- 12 M) was tested in PC12 cell culture after hypoxia and in gerbils after transient occlusion of bilateral common carotid artery. In PC12 culture the cell death was visualized by PI staining. The level of reactive oxygen species was measured by the Cerium method, and the mitochondrial membrane integrity was labeled by JC1 staining. Apoptotic neurons were counted on formaldehyde fixed gerbil brain slices after TUNEL and caspase-3 immune-staining - NIKON/BIORAD confocal microscopy was used for the quantitative analysis. Results: DNO treatment significantly decreased the frequency of cell death in PC12 cultures after hypoxia, increased the mitochondrial transmembrane potential (ΔYm) and decreased the ROS production. In the CA2 regions of gerbil hippocampus, we found significantly less apoptotic neurons than in the untreated controls. Conclusion: Transient hypoxia or ischemia induced cell damage could be diminished by DNO. This (-)deprenyl metabolite is an active cell protective molecule.

Original languageEnglish
Pages (from-to)182-186
Number of pages5
JournalJournal of the Neurological Sciences
Volume283
Issue number1-2
DOIs
Publication statusPublished - Aug 15 2009

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Selegiline
Gerbillinae
PC12 Cells
Brain Ischemia
Wounds and Injuries
Mitochondrial Membranes
Staining and Labeling
Neurons
Cell Death
Cerium
Common Carotid Artery
Monoamine Oxidase
In Situ Nick-End Labeling
deprenyl-N-oxide
Confocal Microscopy
Caspase 3
Membrane Potentials
Formaldehyde
Reactive Oxygen Species
Hippocampus

Keywords

  • Apoptosis
  • Deprenyl
  • Deprenyl-N-oxide
  • Gerbil stroke model
  • Neuroprotection
  • PC-12

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

(-)Deprenyl-N-oxide, a (-)deprenyl metabolite, is cytoprotective after hypoxic injury in PC12 cells, or after transient brain ischemia in gerbils. / Szilágyi, Géza; Simon, László; Wappler, Edina; Magyar, K.; Nagy, Zoltán.

In: Journal of the Neurological Sciences, Vol. 283, No. 1-2, 15.08.2009, p. 182-186.

Research output: Contribution to journalArticle

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abstract = "Background and aims: (-)-Deprenyl (selegiline) possesses cyto-protective effect in a much lower concentration, than it is needed to inhibit MAO-B activity. In permanent MCA occlusion stroke model in rats, the infarct volume and the number of apoptotic neurons in the penumbra region were decreased by low concentration (-)deprenyl treatment. Augmented Bcl-2 protein expression was documented as the responsible factor of this effect. The stabilization of mitochondrial membrane and diminished ROS production are the further possible consequences of (-)deprenyl treatment. It is not clear however that (-)deprenyl, or its metabolites are the acting neuroprotective molecules in the hypoxic/ischemic conditions. We report here the possible cyto-protective effect of deprenyl-N-oxide (DNO), a recently synthesized (-)deprenyl metabolite. Methods: DNO in a very low dose (10- 5,- 8,- 12 M) was tested in PC12 cell culture after hypoxia and in gerbils after transient occlusion of bilateral common carotid artery. In PC12 culture the cell death was visualized by PI staining. The level of reactive oxygen species was measured by the Cerium method, and the mitochondrial membrane integrity was labeled by JC1 staining. Apoptotic neurons were counted on formaldehyde fixed gerbil brain slices after TUNEL and caspase-3 immune-staining - NIKON/BIORAD confocal microscopy was used for the quantitative analysis. Results: DNO treatment significantly decreased the frequency of cell death in PC12 cultures after hypoxia, increased the mitochondrial transmembrane potential (ΔYm) and decreased the ROS production. In the CA2 regions of gerbil hippocampus, we found significantly less apoptotic neurons than in the untreated controls. Conclusion: Transient hypoxia or ischemia induced cell damage could be diminished by DNO. This (-)deprenyl metabolite is an active cell protective molecule.",
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AU - Simon, László

AU - Wappler, Edina

AU - Magyar, K.

AU - Nagy, Zoltán

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