Wu Jing, Zhang Xuan, Nauta Haring J, Lin Qing, Li Junfa, Fang Li
Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Biochem Biophys Res Commun. 2008 Nov 28;376(4):781-6. doi: 10.1016/j.bbrc.2008.09.073. Epub 2008 Sep 24.
Trigeminal nerve fibers in nasal and oral cavities are sensitive to various environmental hazardous stimuli, which trigger many neurotoxic problems such as chronic migraine headache and trigeminal irritated disorders. However, the role of JNK kinase cascade and its epigenetic modulation of histone remodeling in trigeminal ganglion (TG) neurons activated by environmental neurotoxins remains unknown. Here we investigated the role of JNK/c-Jun cascade in the regulation of acetylation of H3 histone in TG neurons following in vitro stimulation by a neuro-inflammatory agent, mustard oil (MO). We found that MO stimulation elicited JNK/c-Jun pathway significantly by enhancing phospho-JNK1, phospho-c-Jun expression, and c-Jun activity, which were correlated with an elevated acetylated H3 histone in TG neurons. However, increases in phospho-c-Jun and c-Jun activity were significantly blocked by a JNK inhibitor, SP600125. We also found that altered H3 histone remodeling, assessed by H3 acetylation in triggered TG neurons, was reduced by SP600125. The study suggests that the activated JNK signaling in regulation of histone remodeling may contribute to neuro-epigentic changes in peripheral sensory neurons following environmental neurotoxic exposure.
鼻腔和口腔中的三叉神经纤维对各种环境有害刺激敏感，这些刺激会引发许多神经毒性问题，如慢性偏头痛和三叉神经激惹性疾病。然而，JNK激酶级联及其对组蛋白重塑的表观遗传调控在环境神经毒素激活的三叉神经节（TG）神经元中的作用仍不清楚。在此，我们研究了在体外经神经炎症剂芥子油（MO）刺激后，JNK/c-Jun级联在TG神经元中对H3组蛋白乙酰化调控的作用。我们发现，MO刺激通过增强磷酸化JNK1、磷酸化c-Jun表达和c-Jun活性，显著激活JNK/c-Jun通路，这与TG神经元中乙酰化H3组蛋白水平升高相关。然而，JNK抑制剂SP600125可显著阻断磷酸化c-Jun和c-Jun活性的增加。我们还发现，通过触发TG神经元中的H3乙酰化评估的H3组蛋白重塑改变，可被SP600125降低。该研究表明，激活的JNK信号在组蛋白重塑调控中可能导致环境神经毒素暴露后外周感觉神经元的神经表观遗传变化。
