title: Vascular endothelial growth factor protects post-ganglionic sympathetic neurones from the detrimental effects of hydrogen peroxide by increasing catalase.
abstract: OBJECTIVE
  Vascular production of hydrogen peroxide (H(2)O(2)) is implicated in the development and progression of vascular disease. Hydrogen peroxide also promotes neuronal degeneration, which suggests that vascular H(2)O(2) would promote degeneration of perivascular sympathetic nerves. Vascular cells also produce vascular endothelial growth factor (VEGF), which could protect perivascular nerves from the detrimental effects of H(2)O(2) . The aim of this study was to test these hypotheses.
  
  
  METHODS
  The effects of H(2)O(2) and VEGF on neuronal survival and noradrenaline uptake were studied in cultures of rat post-ganglionic sympathetic neurones. Western analyses of catalase and growth associated protein 43 were performed and reactive oxygen species (ROS) were measured using the fluorescent indicator 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate, acetyl ester.
  
  
  RESULTS
  Hydrogen peroxide (30 μm) decreased the survival of post-ganglionic sympathetic neurones (57.8 ± 4.8% of control) and decreased noradrenaline uptake into the neurones (14 ± 6% of control). Hyperglycaemia, which is known to increase H(2)O(2), also decreased survival (31.4 ± 12% of control) and noradrenaline uptake (42 ± 18.4% of control). VEGF reduced the effects of H(2)O(2) (94.3 ± 12% of control) and hyperglycaemia (83.5 ± 23.6% of control) on survival. VEGF increased catalase, a primary determinant of intracellular concentrations of H(2)O(2) , and decreased H(2)O(2) -induced increases in ROS.
  
  
  CONCLUSIONS
  These results indicate that VEGF protects post-ganglionic sympathetic neurones from the detrimental effects of H(2)O(2). Our data suggest that an increase in catalase is the mechanisms underlying this neuroprotection.
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington, USA. deborah.damon@uvm.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Damon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016877:Oxidants; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide; D002374:Catalase