regulation of the proteasome by ampk in endothelial cells the role of o-glcnac transferase (ogt)蛋白酶体的调控ampk在内皮细胞的作用o-glcnac转移酶(油气痕迹).pdfVIP

Regulation of the Proteasome by AMPK in Endothelial Cells: The Role of O-GlcNAc Transferase (OGT) 1 2 3,4,5 2 Jian Xu , Shuangxi Wang , Benoit Viollet , Ming-Hui Zou * 1 Division of Endocrinology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 2 Molecular Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 3 Inserm, U1016, Institut Cochin, ´ Paris, France, 4 Cnrs, UMR 8104 Paris, France, 5 Universite Paris Descartes, Paris, France Abstract 26S proteasome is a macromolecular multi-subunit complex responsible for recognizing, unfolding, and ultimately destroying proteins. It remains poorly understood how 26S proteasome activity is regulated. The present study was to investigate if AMP-activated protein kinase (AMPK) functions as a physiological suppressor of the 26S proteasome in endothelial cells. 26S proteasome assembly, activity, and O-GlcNAcylation of P700 were assayed in cultured human umbilical vein endothelial cells (HUVEC) and mouse aortas isolated from C57BL6 wild type and AMPKa2 knockout mice with or without being exposed to selective AMPK activators or inhibitors. Pharmacological and genetic activation of AMPK effectively suppresses 26S proteasomes in endothelial cells. Conversely, inactivation of AMPK either pharmacologically or genetically increases 26S proteasome activity; furthermore, the inactivation decreases the O-GlcNAcylation of PA700/S10B (the regulatory complex in 26S proteasomes) and increases the assembly of 26S proteasomes. In con