title: Neuroprotection by nicotine against colchicine-induced apoptosis is mediated by PI3-kinase--Akt pathways.
abstract: Although nicotine is known to protect against β-amyloid (Aβ)-induced neurotoxicity, the effect of nicotine on colchicine-induced neurotoxicity remains unknown. Colchicine is a microtubule-interfering agent and is able to induce neural apoptosis. Here we investigated whether nicotine exhibits similar neuroprotective effects and the mechanism against colchicine-induced neurotoxicity of the primarily cultured cortical neurons. In this study, we investigated the effect of nicotine on the protection of neurons against colchicine damage and evaluated the associated intracellular signaling pathways. Nicotine-induced protection was blocked by an α7 nicotinic acetylcholine receptors (nAChRs) antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. These results suggest that the neuroprotective effects of nicotine are mediated by the α7 nAChRs and PI3K-Akt signaling pathway. In addition, we reveal that blockade of p38 and JNK (c-Jun N-terminal kinase) signaling increased Akt signaling, thus enhancing the survival of cell treatment with colchicine. On the other hand, inhibition of constitutively active Akt enhanced p38 or JNK signaling phosphorylation. These data suggested that crosstalk between PI3K Akt and p38 or JNK signaling pathways contributed to nicotine against colchicine-induced cytotoxicity.
authors.affiliation: Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Cheng
authors.forename: Qiao
authors.initials: Q
authors.lastname: Su
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Ruzhu
authors.initials: R
authors.lastname: Chen
authors.forename: Xuelan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002038:Bungarotoxins / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D003078:Colchicine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D018696:Neuroprotective Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003078:Colchicine