Nitric oxide enhances MPP+ inhibition of complex I

FEBS Letters

Cleeter, M.W.J.¹  Cooper, J.M.¹  Schapira, A.H.V.¹ 

[1] University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK

关键词: Mitochondrion;    Nitric oxide;    Complex I;    1-Methyl-4-phenylpyridinium;    Parkinson's disease;   

DOI  :  10.1016/S0014-5793(01)02763-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

There is evidence that 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) toxicity is mediated through both inhibition of mitochondrial complex I and free radical generation. 7-Nitroindazole protects against MPTP toxicity in vitro and in vivo, and this appears to be related to its inhibition of nitric oxide (NO) synthase. We now show that the NO generator, glutathione-N-oxide, enhances the inhibitory action of 1-methyl-4-phenylpyridinium (MPP⁺) on complex I activity in brain submitochondrial particles. We propose that the NO-induced reversible inhibition of complex IV (cytochrome oxidase) potentiates the MPP⁺-induced irreversible free radical-mediated inhibition of complex I. Thus, NO may ‘prime’ the respiratory chain to the effects of MPP⁺. These data provide evidence for an interaction between NO and MPP⁺ at the level of the respiratory chain.

【 授权许可】

Unknown