Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells.
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, [3H]epibatidine binding sites for nicotinic receptor and [3H]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 microM) rescued the decreased rates of cell viability and inhibited the production of lipid peroxidation resulted from H(2)O(2) and Abeta in the cultured cells. Significant increases in [3H]epibatidine binding sites were observed in PC12 cells exposed to nicotine, while no change was detected in [3H]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.
Guan
Zhi-Zhong
ZZ
Division of Molecular Neuropharmacology, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Karolinska Institutet, Huddinge University Hospital B84, SE-141 86 Stockholm, Sweden. zhizhong.guan@neurotec.ki.se
Yu
Wen-Feng
WF
Nordberg
Agneta
A
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D015227:Lipid Peroxidation; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D011725:Pyridines / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D014316:Tritium
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018696:Neuroprotective Agents; D011725:Pyridines; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; C082748:epibatidine