title: Role of myosin light chain and myosin light chain kinase in advanced glycation end product-induced endothelial hyperpermeability in vitro and in vivo.
abstract: We have previously reported that advanced glycation end products activated Rho-associated protein kinase and p38 mitogen-activated protein kinase, causing endothelial hyperpermeability. However, the mechanisms involved were not fully clarified. Here, we explored the role of myosin light chain kinase in advanced glycation end product-induced endothelial hyperpermeability. Myosin light chain phosphorylation significantly increased by advanced glycation end products in endothelial cells in a time- and dose-dependent manner, indicating that myosin light chain phosphorylation is involved in the advanced glycation end product pathway. Advanced glycation end products also induced myosin phosphatase-targeting subunit 1 phosphorylation, and small interfering RNA knockdown of the receptor for advanced glycation end products, or blocking myosin light chain kinase with its inhibitor, ML-7, or small interfering RNA abated advanced glycation end product-induced myosin light chain phosphorylation. Advanced glycation end product-induced F-actin rearrangement and endothelial hyperpermeability were also diminished by inhibition of receptor for advanced glycation end product or myosin light chain kinase signalling. Moreover, inhibiting myosin light chain kinase with ML-7 or blocking receptor for advanced glycation end product with its neutralizing antibody attenuated advanced glycation end product-induced microvascular hyperpermeability. Our findings suggest a novel role for myosin light chain and myosin light chain kinase in advanced glycation end product-induced endothelial hyperpermeability.
authors.affiliation: Key Laboratory of Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China Department of Nephrology, The Third Hospital of Zhengzhou, Zhengzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key Laboratory of Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key Laboratory of Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.
authors.forename: Weiju
authors.initials: W
authors.lastname: Wang
authors.affiliation: Postdoctoral Workstation, Huabo Bio-Pharmaceutical Research Institute, Guangzhou, China.
authors.forename: Bingling
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Department of ICU, General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Su
authors.affiliation: Postdoctoral Workstation, Huabo Bio-Pharmaceutical Research Institute, Guangzhou, China Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Department of ICU, General Hospital of Guangzhou Military Command, Guangzhou, China 994606548@qq.com.
authors.forename: Qiulin
authors.initials: Q
authors.lastname: Xu
mesh_terms: D001381:Azepines / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001381:Azepines; D017127:Glycation End Products, Advanced; D018994:Myosin Light Chains; D009281:Naphthalenes; D000067759:Receptor for Advanced Glycation End Products; C070571:ML 7; D009219:Myosin-Light-Chain Kinase
keywords: Advanced glycation end products; endothelial hyperpermeability; myosin light chain kinase; receptor for advanced glycation end products