title: Role of PON in anoxia-reoxygenation injury: a Drosophila melanogaster transgenic model.
abstract: BACKGROUND
  Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This enzyme has been implicated in lowering the risk of cardiovascular disease. Anoxia-reoxygenation and oxidative stress are important elements in cardiovascular and cerebrovascular disease. However, the role of PON1 in anoxia-reoxygenation or anoxic injury is unclear. We hypothesize that PON1 prevents anoxia-reoxygenation injury. We set out to determine whether PON1 expression in Drosophila melanogaster protects against anoxia-reoxygenation (A-R) induced injury.
  
  
  METHODS
  Wild type (WT) and transgenic PON1 flies were exposed to anoxia (100% Nitrogen) for different time intervals (from 1 to 24 hours). After the anoxic period, flies were placed in room air for reoxygenation. Activity and survival of flies was then recorded.
  
  
  RESULTS
  Within 5 minutes of anoxia, all flies fell into a stupor state. After reoxygenation, survivor flies resumed activity with some delay. Interestingly, transgenic flies recovered from stupor later than WT. PON1 transgenic flies had a significant survival advantage after A-R stress compared with WT. The protection conferred by PON1 expression was present regardless of the age or dietary restriction. Furthermore, PON1 expression exclusively in CNS conferred protection.
  
  
  CONCLUSIONS
  Our results support the hypothesis that PON1 has a protective role in anoxia-reoxygenation injury, and its expression in the CNS is sufficient and necessary to provide a 100% survival protection.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Caraballo
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Borcherding
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Rector
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Emma
authors.initials: E
authors.lastname: Hornick
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Stoltz
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Comellas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D043303:Aryldialkylphosphatase