title: AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun.
abstract: The process of Schwann cells (SCs) forming a sheath around axons is termed as myelination, which plays a pivotal role for proper physiological function in the peripheral nervous system (PNS). The molecular mechanisms regulating SC myelination in the PNS remain to be elucidated. Here, we show that AMP-activated protein kinase (AMPK) in sciatic nerves was gradually decreased during the PNS myelination process. Pharmacological interventions showed that activation of AMPK by AICAR attenuated myelin gene expression in SCs, whereas inhibition of AMPK by Compound C (ComC) or AMPKα1 knockdown stimulated myelin gene expression. Following experiments revealed that c-Jun, a negative modulator of PNS myelination, was activated by AMPK in SCs. The application of ComC in newborn rats markedly downregulated c-Jun expression in sciatic nerves. The lipid and protein synthesis in sciatic nerves was greatly potentiated by ComC. As a consequence, myelin gene expression in sciatic nerves, as well as myelin sheath thickness, were promoted in the ComC-treated rats. All together, our data identify that AMPK is an important negative regulator of Schwann cell myelination in the PNS, and this regulation role may rely on c-Jun activation.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Peng
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Meihong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Geratology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China. yangym@ntu.edu.cn.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China. suncheng1975@ntu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009186:Myelin Sheath / Q000201:enzymology*; D017933:Peripheral Nervous System / Q000201:enzymology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D055372:AMP-Activated Protein Kinases
keywords: AICAR; AMPK; Compound C; Myelination; Schwann cells; c-Jun