H₂O₂-mediated RAGE up-regulation on A[beta]-induced superoxide in cerebral endothelial cells

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The up-regulation of receptor for advanced glycation (RAGE) product has been implicated in the pathophysiology of Alzheimer's disease (AD). Elevated H2O2 is known to be toxic to neuronal cells, astrocytes and cerebral endothelial cells (CECs). In this study, elevated H2O2 caused up-regulation of RAGE in these three types of cells. RAGE would cause damage to central neuron system (CNS) by transfer A[beta] through blood brain barrier and the activation of NADPH oxidase which can release more oxygen ion. The overproduction of reactive oxygen species (ROS) would induce more RAGE. The activation of cPLA2 in CNS and overexpression of p-cPLA2 indicate the accumulation of ROS which could cause damage and change in cell membrane, or even lead to cell death. Hydrogen peroxide inhibited the production of A[beta]-induced superoxide and the activation of cPLA2 in this research.