title: JNK1 regulates histone acetylation in trigeminal neurons following chemical stimulation.
abstract: 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.
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Haring J
authors.initials: HJ
authors.lastname: Nauta
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Fang
mesh_terms: D000107:Acetylation; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002478:Cells, Cultured; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009149:Mustard Plant / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D010938:Plant Oils / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D006657:Histones; D009498:Neurotoxins; D010938:Plant Oils; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048055:Mitogen-Activated Protein Kinase 8; C027793:mustard oil