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  • Title: [Changes and regulatory mechanism of tight junction proteins in in vitro model of lead-induced blood-brain barrier injury].
    Author: Xu Y, Che H, Liu M, Ke T, Ma Y, Chen J, Hao X.
    Journal: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi; 2013 Nov; 29(11):1141-6. PubMed ID: 24200059.
    Abstract:
    OBJECTIVE: To clarify the relationship between the expressions of tight junction (TJ) proteins and the changes of MAPK, AKT signaling pathways in the process of lead-induced blood-brain barrier (BBB) injury in vitro and observe the regulatory mechanisms of related signaling pathway inhibitors. METHODS: The in vitro model of lead-induce BBB injury was established using Transwell™ chamber co-culture system of human umbilical vein endothelium-derived ECV304 cells and rat glioma C6 cells. The system was supplemented with different concentrations of PbC4H6O4. The transendothelial electrical resistance (TEER) and permeability of FITC-labeled dextran were tested to evaluate the changes of permeability of in vitro BBB cell model. The expressions and locations of TJ proteins (ZO-1, occludin and claudin-5) were determined by Western blotting and immunocytochemical staining, respectively. Signaling pathway inhibitors were used to clarify the causal relation between TJ protein expressions and signaling pathways. RESULTS: Lead inhibited ECV304 growth and this inhibition was time- and dose-dependent (P<0.05). TEER value decreased and the permeability of FITC-labeled dextran increased significantly as the time of lead exposure went by (P<0.05). Western blotting showed that the expressions of ZO-1, occludin and claudin-5 were significantly reduced after 2.5 μmol/L lead treatment (P<0.05); the phosphorylation levels of ERK1/2, JNK, p38, AKT473 and AKT308 were elevated significantly (P<0.05); ERK1/2 inhibitor PD98059 and PI3K inhibitor LY294002 reversed the lead effects. These results suggested that lead could inhibit the TJ protein expressions through the ERK1/2 and PI3K/AKT pathways. CONCLUSION: The TJ proteins are important target molecules of lead-induced structural and functional damage of BBB. The MAPK and PI3K/AKT signal transduction pathways are involved in the regulation on the expressions of TJ proteins.
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