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Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats.
Toxicology. 2011 Jul 11; 285(1-2):31-8.T

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+Show Affiliations

Department of Radiation Medicine, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21501651

Citation

Qiu, Lian-Bo, et al. "Synthetic Gelatinases Inhibitor Attenuates Electromagnetic Pulse-induced Blood-brain Barrier Disruption By Inhibiting Gelatinases-mediated ZO-1 Degradation in Rats." Toxicology, vol. 285, no. 1-2, 2011, pp. 31-8.
Qiu LB, Zhou Y, Wang Q, et al. Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats. Toxicology. 2011;285(1-2):31-8.
Qiu, L. B., Zhou, Y., Wang, Q., Yang, L. L., Liu, H. Q., Xu, S. L., Qi, Y. H., Ding, G. R., & Guo, G. Z. (2011). Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats. Toxicology, 285(1-2), 31-8. https://doi.org/10.1016/j.tox.2011.03.019
Qiu LB, et al. Synthetic Gelatinases Inhibitor Attenuates Electromagnetic Pulse-induced Blood-brain Barrier Disruption By Inhibiting Gelatinases-mediated ZO-1 Degradation in Rats. Toxicology. 2011 Jul 11;285(1-2):31-8. PubMed PMID: 21501651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats. AU - Qiu,Lian-Bo, AU - Zhou,Yan, AU - Wang,Qi, AU - Yang,Long-Long, AU - Liu,Hai-Qiang, AU - Xu,Sheng-Long, AU - Qi,Yu-Hong, AU - Ding,Gui-Rong, AU - Guo,Guo-Zhen, Y1 - 2011/04/08/ PY - 2011/02/03/received PY - 2011/03/28/revised PY - 2011/03/31/accepted PY - 2011/4/20/entrez PY - 2011/4/20/pubmed PY - 2011/7/20/medline SP - 31 EP - 8 JF - Toxicology JO - Toxicology VL - 285 IS - 1-2 N2 - 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. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/21501651/Synthetic_gelatinases_inhibitor_attenuates_electromagnetic_pulse_induced_blood_brain_barrier_disruption_by_inhibiting_gelatinases_mediated_ZO_1_degradation_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(11)00125-9 DB - PRIME DP - Unbound Medicine ER -