title: Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction.
abstract: OBJECTIVE
  The present study investigated the effects of ZnCl₂ and MnCl₂ supplementations on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction.
  
  
  METHODS
  Fluorescence detection was used to monitor the Maillard reaction. Inductively coupled plasma optical emission spectroscopy was used to test cellular zinc and manganese levels. Real-time reverse transcription polymerase chain reaction and western blot were used to analyze the expression of endothelial nitric oxide synthase (eNOS), nuclear transcription factor kappa B (NF-κB), and receptor for AGEs (RAGE). Intracellular reactive oxygen species (ROS) and nitric oxide (NO) production, NOS activity were determined by fluorescent probe assay, superoxide dismutase (SOD) activity was determined by water soluble tetrazolium salt assay.
  
  
  RESULTS
  MnCl₂ showed excellent inhibitory effect on AGEs formation. Primary cultured bovine aortic endothelial cells (BAECs) were exposed to AGEs for 30 min, followed by trace element treatments. Cell viability and the zinc levels declined due to AGEs exposure, which were improved with the supplementations of ZnCl₂ and MnCl₂. Furthermore, ZnCl₂ supplementation effectively enhanced intracellular NO production, elevated eNOS expression and enzymatic activity, and down-regulated NF-κB activation and RAGE expression. MnCl₂ dose-dependently impaired ROS formation, down-regulated NF-κB protein expression and nuclear translocation, as well as restored Mn-SOD enzymatic capability.
  
  
  CONCLUSIONS
  Our findings suggested that trace elements relevant to diabetic, such as zinc and manganese played different roles in the formation of AGEs. Both the elements benefited the AGEs-injured BAECs through different mechanisms.
authors.affiliation: School of Life Science, East China Normal University, Shanghai 200062, People's Republic of China.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Pang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Huangjian
authors.initials: H
authors.lastname: Yang
authors.forename: Weijing
authors.initials: W
authors.lastname: Qu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology*; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D008345:Manganese; D015032:Zinc