Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells
Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells
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DOI：
10.1016/s0197-0186(03)00009-3
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发表时间：
2003-08-01
影响因子：
4.2
通讯作者：
Nordberg, A
中科院分区：
文献类型：
--
作者：
Guan, ZZ;Yu, WF;Nordberg, A
为了研究尼古丁与氧化应激或神经保护作用的关系，将尼古丁、β-淀粉样肽（Abeta（25-35））、自由基诱导剂和抗氧化剂分别或联合作用于分化的PC 12细胞。3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）还原、脂质过氧化、烟碱受体的[H-3]地棘蛙素结合位点和毒蕈碱受体的[H-3]奎宁环二苯甲酸酯（QNB）结合位点。仅在高浓度尼古丁（1和10 mM）处理时观察到PC 12细胞MTT还原的显著降低和脂质过氧化作用的增加，而维生素E（VitE），一种抗氧化剂，可以防止神经毒性作用。此外，低剂量尼古丁（10 μ M）可挽救细胞活力下降的速率，并抑制培养细胞中H_2O_2和Abeta引起的脂质过氧化反应的产生。在暴露于尼古丁的PC 12细胞中观察到[H-3]地棘蛙素结合位点的显著增加，而在[H-3]QNB中未检测到变化。由于Abeta的毒性而导致的烟碱受体结合位点数量的减少可通过添加低浓度的尼古丁来防止。尼古丁治疗可能对氧化应激和神经保护发挥双重作用，其中这些作用取决于所用药物剂量及其作用机制的差异，这是合理的。通常，高剂量的尼古丁可诱导神经毒性并刺激氧化应激，而合理的低浓度可作为抗氧化剂并在神经保护作用中发挥重要作用。(C)2003爱思唯尔科技有限公司版权所有。
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.