1‐Methyl‐4‐phenyl‐2,3‐dihydropyridinium is transformed by ubiquinone to the selective nigrostriatal toxin 1‐methyl‐4‐phenylpyridinium

FEBS Letters

Niki, Etsuo¹  Noguchi, Noriko¹  Xu, Yuexian¹  Shi, Honglian¹ 

[1] Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Tokyo 153-8904, Japan

关键词: 1-Methyl-4-phenyl-1;    2;    3;    6-tetrahydropyridine;    1-Methyl-4-phenyl-2;    3-dihydropyridinium;    Coenzyme Q;    Ubiquinone;    Monoamine oxidase;    Rat brain synaptosome;    Parkinson's disease;    EC;    electrochemical;    HPLC;    high performance liquid chromatography;    MAO;    monoamine oxidase;    MPDP+;    1-methyl-4-phenyl-2;    3-dihydropyridinium;    MPP+;    1-methyl-4-phenylpyridinium;    MPTP;    1-methyl-4-phenyl-1;    2;    3;    6-tetrahydropyridine;   

DOI  :  10.1016/S0014-5793(99)01444-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have studied the interaction of coenzyme Q with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolites, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP⁺) and 1-methyl-4-phenylpyridinium (MPP⁺), the real neurotoxin to cause Parkinson's disease. Incubation of MPTP or MPDP⁺ with rat brain synaptosomes induced complete reduction of endogenous ubiquinone-9 and ubiquinone-10 to corresponding ubiquinols. The reduction occurred in a time- and MPTP/MPDP⁺ concentration-dependent manner. The reduction of ubiquinone induced by MPDP⁺ went much faster than that by MPTP. MPTP did not reduce liposome-trapped ubiquinone-10, but MPDP⁺ did. The real toxin MPP⁺ did not reduce ubiquinone in either of the systems. The reduction by MPTP but not MPDP⁺ was completely prevented by pargyline, a type B monoamine oxidase (MAO-B) inhibitor, in the synaptosomes. The results indicate that involvement of MAO-B is critical for the reduction of ubiquinone by MPTP but that MPDP⁺ is a reductant of ubiquinone per se. It is suggested that ubiquinone could be an electron acceptor from MPDP⁺ and promote the conversion from MPDP⁺ to MPP⁺ in vivo, thus accelerating the neurotoxicity of MPTP.

【 授权许可】

Unknown