Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism.
OBJECTIVE
In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis.


METHODS
Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax.


RESULTS
Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In.


CONCLUSIONS
The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.
Oksala
Niku K J
NK
Departments of Surgery, Kuopio University Hospital, Kuopio.
Oksala
Anni
A
Paavonen
Timo
T
Alhava
Esko
E
Paimela
Hannu
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000293:injuries* / Q000378:metabolism; D006168:Guinea Pigs; D018869:Heat-Shock Response / Q000502:physiology*; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011794:Quercetin / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*; D051028:bcl-2-Associated X Protein
D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016718:Arachidonic Acid; D003513:Cycloheximide; D011794:Quercetin; D007213:Indomethacin