(-)-Deprenyl protection of 1-methyl-4 phenylpyridium ion (MPP+)-induced apoptosis independent of MAO-B inhibition.
Selective loss of central dopaminergic neurons in vitro and in vivo can be initiated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through its metabolite phenylpyridium ion (MPP+). Such MPTP-mediated cytotoxicity can be blocked by (-)-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, but the exact mechanisms of MPP(+)-induced cytotoxicity and (-)-Deprenyl's protection against such neurotoxicity are not fully understood. Using a hybrid clone MES 23.5, a dopaminergic cell line that does not contain MAO-B, we document that MPP+ induces apoptotic cell death. Application of (-)-Deprenyl at concentrations of 0.1-10 microM significantly reduces MPP(+)-induced apoptosis in MES 23.5 cells; (-)-Deprenyl at higher concentrations (> 100 microM) that completely inhibit MAO-B activity, however, induces apoptosis. Pretreatment with N-(2-aminoethyl)-p-chlorobenzamide (Ro 16-6491), a selective MAO-B inhibitor, does not protect MES 23.5 cells against MPP(+)-induced cell death. These results suggest that the protective action of (-)-Deprenyl against MPP+ neuro-toxicity in dopaminergic cell line may be independent of the inhibition of MAO-B.
Le
W
W
Baylor College of Medicine, Department of Neurology, Houston, TX 77030, USA.
Jankovic
J
J
Xie
W
W
Kong
R
R
Appel
S H
SH
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D006822:Hybrid Cells / Q000187:drug effects*; D008995:Monoamine Oxidase / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D012642:Selegiline / Q000494:pharmacology*
D012642:Selegiline; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium