Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells

被引:149
作者
Guan, ZZ [1 ]
Yu, WF [1 ]
Nordberg, A [1 ]
机构
[1] Huddinge Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Div Mol Neuropharmacol,Occupat Therapy & Elderly, SE-14186 Stockholm, Sweden
关键词
lipid peroxidation; MTT reduction; nicotine; nicotinic receptors; PC12; cells;
D O I
10.1016/S0197-0186(03)00009-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In order to identify the properties of nicotine in relation to oxidative stress or neuroprotection, differentiated PC12 cells were treated with nicotine, beta-amyloid peptide (Abeta(25-35)), free radical inducer and antioxidant by a separate addition or a combination way. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lipid peroxidation, [H-3]epibatidine binding sites for nicotinic receptor and [H-3]quinuclidinyl benzilate (QNB) for muscarinic receptor have been detected. The significant decrease of MTT reduction and increase of lipid peroxidation in PC12 cells were only observed at treatments with high concentrations of nicotine (1 and 10 mM), while Vitamin E (VitE), an antioxidant, can prevent the neurotoxic effects. In addition, nicotine in low dosage (10 muM) rescued the decreased rates of cell viability and inhibited the production of lipid peroxidation resulted from H2O2 and Abeta in the cultured cells. Significant increases in [H-3]epibatidine binding sites were observed in PC12 cells exposed to nicotine, while no change was detected in [H-3]QNB. The decreased number of nicotinic receptor binding sites due to the toxicity of Abeta was prevented by the addition of nicotine with low concentration. It is plausible that nicotine treatment may play dual effects on oxidative stress and neuroprotection, in which the effects are dependent on the differences in dosage of the drug used and their mechanisms of action. Generally, high dose of nicotine may induce neurotoxicity and stimulate oxidative stress, while reasonably low concentration may act as an antioxidant and play an important role for neuroprotective effect. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:243 / 249
页数:7
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