(-)-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 μM significantly reduces MPP⁺-induced apoptosis in MES 23.5 cells; (-)-Deprenyl at higher concentrations (> 100 μM) 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⁺ neurotoxicity in dopaminergic cell line may be independent of the inhibition of MAO-B.