Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.
Nicotine reduces beta-amyloidosis and has a beneficial effect against Alzheimer's disease (AD), but the underlying mechanism is not clear. The abnormal interactions of beta-amyloid (Abeta) with metal ions such as copper and zinc are implicated in the process of Abeta deposition in AD brains. In the present study, we investigated the effect of nicotine on metal homeostasis in the hippocampus and cortex of APP(V717I) (London mutant form of APP) transgenic mice. A significant reduction in the metal contents of copper and zinc in senile plaques and neuropil is observed after nicotine treatment. The densities of copper and zinc distributions in a subfield of the hippocampus CA1 region are also reduced after nicotine treatment. We further studied the mechanism of nicotine-mediated effect on metal homeostasis by using SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw). Nicotine treatment decreases the intracellular copper concentration and attenuates Abeta-mediated neurotoxicity facilitated by the addition of copper, and these effects are independent of the activation of nicotinic acetylcholine-receptor. These data suggest that the effect of nicotine on reducing beta-amyloidosis is partly mediated by regulating metal homeostasis.
Zhang
Jie
J
State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, 15 Datun Rd., Chaoyang District, Beijing 100101, Peoples Republic of China.
Liu
Qiang
Q
Chen
Qi
Q
Liu
Nian-Qing
NQ
Li
Fu-Liang
FL
Lu
Zhong-Bing
ZB
Qin
Chuan
C
Zhu
Hua
H
Huang
Yu-Ying
YY
He
Wei
W
Zhao
Bao-Lu
BL
D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D008670:Metals / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C491962:Ccs protein, mouse; D008670:Metals; D018832:Molecular Chaperones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; C000606290:SOD1 protein, human; C078592:amyloid beta-protein (1-40); D009538:Nicotine; D003300:Copper; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1