title: Advanced glycation end products induce moesin phosphorylation in murine brain endothelium.
abstract: Advanced glycation end products (AGEs) have been found to play an important role in the development of diabetes, and AGE levels are correlated with the severity of diabetic complications. We have demonstrated that moesin, a protein linker between actin filaments and the plasma membrane, undergoes phosphorylation of its threonine 558 residue by AGE stimulation in human dermal microvascular endothelial cells through activation of p38 and Rho kinase (ROCK) pathways. In this study, we observed in situ whether AGEs caused phosphorylation of vascular endothelial cells in the brains of AGE-stimulated mice. The animals were injected with AGE-modified mouse serum albumin (AGE-MSA) for 7 consecutive days. Immunohistochemistry was conducted to assess the phosphorylation of moesin in brain vessels. The level of moesin protein phosphorylation was also assessed in cerebral microvessels by western blotting. The effects of p38 and ROCK activation were determined by application of a p38 inhibitor (SB203580) and a ROCK inhibitor (Y27632) at 30 min before each AGE administration. The results showed specific expression of moesin in murine brain vascular endothelial cells. AGE treatment induced a significant increase of threonine 558 phosphorylation in moesin, while inhibition of p38 and ROCK remarkably attenuated the phosphorylation of moesin. The level of moesin protein phosphorylation was also increased in cerebral microvessels, along with an increased permeability of the blood-brain barrier, while inhibition of the p38 and ROCK attenuated these responses. These results demonstrate that AGEs cause the phosphorylation of moesin in murine brain microvascular endothelial cells, with p38 and ROCK being involved in this process.
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, 1023 Shatai Road, Tonghe, Guangzhou 510515, PR China.
authors.forename: Qiaoqin
authors.initials: Q
authors.lastname: Li
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Guo
authors.forename: Xuliang
authors.initials: X
authors.lastname: Huang
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology*; D004347:Drug Interactions / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D008840:Microfilament Proteins; D011725:Pyridines; C108830:Y 27632; C071058:moesin; D013912:Threonine; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580