Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Int J Neurosci. 2012 Jun;122(6):324-32. doi: 10.3109/00207454.2012.657377. Epub 2012 Mar 5.
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.
虽然尼古丁已知可预防β-淀粉样蛋白（Aβ）诱导的神经毒性，但尼古丁对秋水仙碱诱导的神经毒性的影响尚不清楚。秋水仙碱是一种微管干扰剂，能够诱导神经细胞凋亡。在这里，我们研究了尼古丁是否对原代培养的皮质神经元的秋水仙碱诱导的神经毒性具有相似的神经保护作用及其机制。在这项研究中，我们研究了尼古丁对神经元免受秋水仙碱损伤的保护作用，并评估了相关的细胞内信号通路。α7 烟碱型乙酰胆碱受体（nAChRs）拮抗剂和磷酸肌醇 3-激酶（PI3K）抑制剂阻断了尼古丁诱导的保护作用。这些结果表明，尼古丁的神经保护作用是通过α7 nAChRs 和 PI3K-Akt 信号通路介导的。此外，我们揭示了阻断 p38 和 JNK（c-Jun N-末端激酶）信号通路增加了 Akt 信号通路，从而增强了秋水仙碱处理的细胞存活。另一方面，抑制组成型激活的 Akt 增强了 p38 或 JNK 信号通路磷酸化。这些数据表明，PI3K-Akt 和 p38 或 JNK 信号通路之间的串扰有助于尼古丁对抗秋水仙碱诱导的细胞毒性。
