AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase C zeta

作者：Choi Yoon Kyung; Kim Kyu Won^*

来源：FEBS Journal, 2008, 275(9): 2338-2353.

DOI：10.1111/j.1742-4658.2008.06387.x

• AKAP12 (A-kinase anchor protein 12)
• blood-neural barrier
• protein kinase C zeta
• thrombospondin-1
• vascular endothelial growth factor

Interactions between astrocytes and blood vessels are essential for the formation and maintenance of the blood-neural barrier (BNB). Astrocyte-derived A-kinase anchor protein 12 (AKAP12) influences BNB formation, but the mechanism of regulation of BNB functions by AKAP12 is not fully understood. We have defined a new pathway of barriergenesis in human retina microvascular endothelial cells (HRMECs) involving astrocytic AKAP12. Treatment of HRMECs with conditioned media from AKAP12-overexpressing astrocytes reduced phosphorylation of protein kinase C zeta (PKC zeta), decreased the levels of vascular endothelial growth factor (VEGF) mRNA and protein, and increased thrombospondin-1 (TSP-1) levels, which led to antiangiogenesis and barriergenesis. Transfection of a small interference RNA targeting PKC zeta decreased VEGF levels and increased TSP-1 levels in HRMECs. Rho is a putative downstream signal of PKC zeta, and inhibition of Rho kinase with a specific inhibitor, Y27632, decreased VEGF levels and increased TSP-1 levels. We therefore suggest that AKAP12 in astrocytes differentially regulates the expression of VEGF and TSP-1 via the inhibition of PKC zeta phosphorylation and Rho kinase activity in HRMECs.

• 出版日期2008-5