title: Effects and mechanisms of melatonin on the proliferation and neural differentiation of PC12 cells.
abstract: Melatonin, a lipophilic molecule that is mainly synthesized in the pineal gland, performs various neuroprotective functions. However, the detailed role and mechanisms of promoting neuronal differentiation remains limited. This study demonstrated that 10 μM melatonin led to significant increases in the proliferation and neurite outgrowth of PC12 cells. Increased expression of microtubule-associated protein 2 (MAP2, a neuron-specific protein) was also observed. However, luzindole (melatonin receptor antagonist) and PD98059 (MEK inhibitor) attenuated these increases. LY294002 (AKT inhibitor) inhibited melatonin-mediated proliferation in PC12 cells and did not affect melatonin-induced neural differentiation. The expression of p-ERK1/2/ERK1/2 was increased by melatonin treatment for 14 days in PC12 cells, whereas luzindole or PD98059 reduced the melatonin-induced increase. These results suggest that the activation of both the MEK/ERK and PI3K/AKT signaling pathways could potentially contribute to melatonin-mediated proliferation, but that only the MEK/ERK pathway participates in the melatonin-induced neural differentiation of PC12 cells. Altogether, our study demonstrates for the first time that melatonin may exert a positive effect on neural differentiation via melatonin receptor signalling and that the MEK/ERK1/2 signalling may act down stream from the melatonin pathway.
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China. Electronic address: lymzq@126.com.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Qiongxia
authors.initials: Q
authors.lastname: Lv
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Shi
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D008550:Melatonin
keywords: AKT; ERK1/2; Melatonin; Neuronal differentiation; PC12 cells