title: Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats.
abstract: Previously we found that exposure to electromagnetic pulse (EMP) induced an increase in blood-brain-barrier (BBB) permeability and the degradation of tight junction protein ZO-1 in rats. Matrix metalloproteinases (MMPs), in particular gelatinases (MMP-2 and MMP-9), play a key role in degradation of tight junction proteins, are known mediators of BBB compromise. We hypothesized that the degradation of ZO-1 by gelatinases contributed to EMP-induced BBB opening. To test this hypothesis, the mRNA level of ZO-1, protein levels of MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) were detected in rat cerebral cortex after exposing rats to EMP at 200 kV/m for 200 pulses. It was found that the mRNA level of ZO-1 was unaltered at different time points after EMP exposure. The protein levels of MMP-2 and MMP-9 significantly increased at 3 h and 0.5 h, respectively. However, TIMP-1 (inhibitor of MMP-9) and TIMP-2 (inhibitor of MMP-2) only moderately increased after EMP exposure. In addition, in situ zymography results showed that the gelatinase activity increased in cerebral microvessels at 3 h after EMP exposure. When rats were treated with gelatinases inhibitor (SB-3CT) before EMP exposure, the EMP-induced BBB opening was attenuated and the ZO-1 degradation was reversed. Our results suggested that EMP-induced BBB opening was related to gelatinase mediated ZO-1 degradation.
authors.affiliation: Department of Radiation Medicine, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Yang
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Liu
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Xu
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Qi
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Ding
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Guo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D004574:Electromagnetic Fields; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C429533:SB 3CT compound; D013450:Sulfones; D019715:Tissue Inhibitor of Metalloproteinase-1; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9