Investigating the receptor-independent neuroprotective mechanisms of nicotine in mitochondria.
J. Biol. Chem.. 2005-06-27; 280(37): 32405-32412
DOI: 10.1074/jbc.m504664200
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1. J Biol Chem. 2005 Sep 16;280(37):32405-12. Epub 2005 Jun 27.
Investigating the receptor-independent neuroprotective mechanisms of nicotine in
mitochondria.
Xie YX(1), Bezard E, Zhao BL.
Author information:
(1)State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics,
Academia Sinica, Beijing, China.
Although nicotine has been associated with a decreased risk of developing
Parkinson disease, the underlying mechanisms are still unclear. By using isolated
brain mitochondria, we found that nicotine inhibited N-methyl-4-phenylpyridine
(MPP(+)) and calcium-induced mitochondria high amplitude swelling and cytochrome
c release from intact mitochondria. Intra-mitochondria redox state was also
maintained by nicotine, which could be attributed to an attenuation of
mitochondria permeability transition. Further investigation revealed that
nicotine did not prevent MPP(+)- or calcium-induced mitochondria membrane
potential loss, but instead decreased the electron leak at the site of
respiratory chain complex I. In the presence of mecamylamine hydrochloride, a
nonselective nicotinic acetylcholine receptor inhibitor, nicotine significantly
postponed mitochondria swelling and cytochrome c release induced by a mixture of
neurotoxins (MPP(+) and 6-hydroxydopamine) in SH-SY5Y cells, suggesting that
there is a receptor-independent nicotine-mediated neuroprotective effect of
nicotine. These results show that interaction of nicotine with mitochondria
respiratory chain together with its antioxidant effects should be considered in
the neuroprotective effects of nicotine.
DOI: 10.1074/jbc.M504664200
PMID: 15985439 [Indexed for MEDLINE]