Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures.
1. Recent studies indicate that neuronal loss in Alzheimer's disease (AD) is accompanied by the deposition of beta-amyloid protein (A beta) in senile plaques. Nicotine as a major component of cigarette smoke has been suggested to have a protective effect for neurons against A beta neurotoxicity. 2. Our present study demonstrates that nicotine protected cultured hippocampal neurons against the A beta-induced apoptosis. Nicotine effectively inhibits apoptosis in hippocampal cultures caused by A beta(25-35) or A beta(1-40) treatment and increase of caspase activity induced by A beta(25-35) or A beta(1-40). 3. Measurements of cellular oxidation and intracellular free Ca(2+) showed that nicotine suppressed A beta-induced accumulation of free radical and increase of intracellular free Ca(2+). 4. Cholinergic antagonist mecamylamine inhibited nicotine-induced protection against A beta-induced caspase-3 activation and ROS accumulation. 5. The data show that the protection of nicotine is partly via nicotinic receptors. Our results suggest that nicotine may be beneficial in retarding the neurodegenerative diseases such as AD.
Liu
Qiang
Q
Laboratory of Visual Processing Information, Center of Brain & Cognitive Science, Institute of Biophysics, Academia Sinica, Beijing 100101, People's Republic of China.
Zhao
Baolu
B
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008464:Mecamylamine / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D009498:Neurotoxins; D018722:Nicotinic Agonists; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D008464:Mecamylamine; D009538:Nicotine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D002118:Calcium