(-)-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 ca n 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 full y 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 m u M significantly reduces MPP(+)-induced apoptosis in MES 23.5 cells; (-)-Deprenyl at higher concentrations (>100 mu M) that completely inhi bit MAO-B activity, however, induces apoptosis. Pretreatment with N-(2 -aminoethyl)-p-chlorobenzamide (Ro 16-6491), a selective MAO-B inhibit or, does not protect MES 23.5 cells against MPP(+)-induced cell death. These results suggest that the protective action of (-)-Deprenyl agai nst MPP(+) neurotoxicity in dopaminergic cell line may be independent of the inhibition of MAO-B. (C) 1997 Elsevier Science Ireland Ltd.