tailieunhanh - Báo cáo khoa học: AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase Cf

Interactions between astrocytes and blood vessels are essential for the for-mation 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. | ễFEBS Journal AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase Cf Yoon Kyung Choi and Kyu-Won Kim NeuroVascular Coordination Research Center College of Pharmacy and Research Institute of PharmaceuticalSciences SeoulNationalUniversity Korea Keywords AKAP12 A-kinase anchor protein 12 blood-neuralbarrier protein kinase Cf thrombospondin-1 vascular endothelial growth factor Correspondence . Kim NeuroVascular Coordination Research Center College of Pharmacy SeoulNationalUniversity Seoul151-742 Korea Fax 82 2 872 1795 Tel 82 2 880 6988 E-mail qwonkim@ Received 12 November 2007 revised 2 March 2008 accepted 7 March 2008 doi 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 Cf PKCf 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 PKCf decreased VEGF levels and increased TSP-1 levels in HRMECs. Rho is a putative downstream signal of PKCf 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 PKCf phosphorylation and Rho kinase activity in HRMECs. The interaction of astrocytes and blood vessels plays an important role in retinal .