Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2.

摘要: Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin associated with its localization to TJ sites and incorporation into intact assembly. The present study focused on the role lipid rafts polychlorinated biphenyl (PCB)-induced disruption barrier function. Exposure human cells 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) induced dephosphorylation threonine residues displacement from detergent-resistant membrane (DRM)/lipid raft fractions within 1h. Moreover, modulated reduction level through activation matrix metalloproteinase 2 (MMP-2) after 24h PCB153 treatment. Inhibition phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced increased permeability implication PP2A signaling these processes was further defined co-immunoprecipitation caveolin-1, a marker rafts. Indeed, significant MMP-2 observed exposure PCB153. pretreatment inhibitors loss structure prevented increase permeability. Overall, results indicate that raft-associated processes, such as activation, participate function barrier. This contributes better understanding mechanisms leading dysfunction response environmental pollutants, ortho-substituted PCBs.