title: Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals.
abstract: The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38.
authors.affiliation: Servicio de Investigación-BEM, University Hospital Ramón y Cajal-IRYCIS, 28034 Madrid, Spain. m.antonia.martinez@hrc.es.
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Martínez
authors.affiliation: Servicio de Investigación-BEM, University Hospital Ramón y Cajal-IRYCIS, 28034 Madrid, Spain. axumaeso@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Úbeda
authors.affiliation: Departamento de Ingeniería Eléctrica, Electrónica y de Automatización y Física Aplicada, Technical School of Engineering and Industrial Design (ETSID), UPM, 28012 Madrid, Spain. jorge.moreno@upm.es.
authors.forename: Jorge
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Servicio de Investigación-BEM, University Hospital Ramón y Cajal-IRYCIS, 28034 Madrid, Spain. angeles.trillo@hrc.es.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Trillo
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D020935:MAP Kinase Signaling System; D060526:Magnetic Fields / Q000009:adverse effects*; D009447:Neuroblastoma / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK1/2; JNK; NAC; cell cycle; extremely low frequency; magnetic field; neuroblastoma