Low-dose endothelial monocyte-activating polypeptide-II increases permeability of blood-tumor barrier via a PKC-ζ/PP2A-dependent signaling mechanism.

摘要: Our previous study demonstrated that low-dose endothelial monocyte-activating polypeptide-II (EMAP-II) induces blood-tumor barrier (BTB) opening via the RhoA/Rho kinase/protein kinase C (PKC)-α/β signaling pathway and PKC-ζ is involved in this process other mechanisms. In present study, using an vitro BTB model, we detected exact mechanisms by which activation affects EMAP-II-induced hyperpermeability. results showed three types of serine/threonine (Ser/Thr) protein phosphatases (PPs), namely PP1, PP2A, PP2B, were expressed rat brain microvascular cells (RBMECs). There was interaction between PP2A RBMECs. addition, EMAP-II induced a significant increase both expression activity Inhibition with pseudosubstrate inhibitor (PKC-ζ-PI) completely blocked activation. Conversely, inhibition okadaic acid (OA) had no effect on Like PKC-ζ-PI, OA partially prevented hyperpermeability occludin redistribution Neither PKC-ζ-PI nor affected phosphorylation myosin light chain actin cytoskeleton Taken together, our increases permeability activating PKC-ζ/PP2A pathway, consequently leads to disruption TJs impairment function.