title: Heat-shock preconditioning affects restitution of isolated guinea pig gastric mucosa by an arachidonic acid and protein synthesis dependent mechanism.
abstract: BACKGROUND
  Superficial mucosal injury is repaired immediately by a process known as restitution, which is controlled by several factors and is based on cellular migration. Heat-shock preconditioning increases the tolerance of tissue to deep gastric mucosal injury via synthesis of heat-shock proteins. Despite immediate positive effects on the tissue, we have shown that heat-shock preconditioning inhibits restitution of gastric mucosa after subsequent superficial injury in correlation with Hsp70 levels. In addition to heat-shock proteins, heat preconditioning is known to affect eicosanoid pathways. In this study, we explore the role of eicosanoid pathways and protein synthesis in heat-shock-induced inhibition of restitution.
  
  
  METHODS
  Guinea pig gastric mucosa was mounted and perfused in a Ussing chamber (37 degrees C). After heat-shock preconditioning (HS) (42 degrees C) and normothermic recovery, a superficial injury was induced (1.25 mol/L NaCl) followed by a 3-h restitution. Transmucosal electrophysiologic resistance of the tissue (R) was recorded during the experiment. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid as a substrate for eicosanoid pathways; 50 micromol/L quercetin to inhibit the metabolism of arachidonic acid via lipoxygenases, 50 micromol/L indomethacin to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or 150 micromol/L cycloheximide to inhibit de novo protein synthesis. After the experiment, the mucosa was prepared for morphologic analysis and Western blotting.
  
  
  RESULTS
  HS inhibited restitution after NaCl insult and upregulated Hsp70. Exposure of the tissue to quercetin, cycloheximide, arachidonic acid, or to indomethacin overcame the inhibitory effect of HS, which could be pronounced by simultaneous indomethacin and quercetin augmenting expression of Hsp70.
  
  
  CONCLUSIONS
  HS preconditioning inhibits restitution by a mechanism that involves arachidonic acid metabolism and de novo protein synthesis.
authors.affiliation: Dept. of Surgery, Kuopio University Hospital, Finland.
authors.forename: N K J
authors.initials: NK
authors.lastname: Oksala
authors.forename: H
authors.initials: H
authors.lastname: Paimela
authors.forename: E
authors.initials: E
authors.lastname: Alhava
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response / Q000502:physiology*; D006979:Hyperthermia, Induced
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016718:Arachidonic Acid