title: Electromagnetic-pulse-induced activation of p38 MAPK pathway and disruption of blood-retinal barrier.
abstract: The blood-retinal barrier (BRB) is critical for maintaining retina homeostasis and low permeability. In this study, we evaluated the effects of electromagnetic pulse (EMP) exposure on the permeability of BRB, alterations of tight junction (TJ) proteins of BRB and if any, involvement of mitogen-activated protein kinase (MAPK) pathway. Male Sprague-Dawley (SD) rats and RF/6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV/m for 200 pulses. The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue (EB) and endogenous albumin as tracers. The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots. The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin-5, which were correlated with the increased expressions of phospho-p38, phospho-JNK and phospho-ERK and could be blocked when pretreated with p38 MAPK inhibitor. Thus, the results suggested that the alterations of occludin and claudin-5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules.
authors.affiliation: Department of Radiation Medicine and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, China.
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Li
authors.forename: Liang-Mei
authors.initials: LM
authors.lastname: Guo
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Yang
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Zhou
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Guo
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Xie
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Guo
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000528:radiation effects*; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism / Q000528:radiation effects; D004574:Electromagnetic Fields / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D008856:Microscopy, Fluorescence; D062793:Occludin / Q000378:metabolism / Q000528:radiation effects; D010539:Permeability / Q000528:radiation effects; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D062507:Claudin-5; D004791:Enzyme Inhibitors; D062793:Occludin; D005070:Evans Blue