Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart.
BACKGROUND
Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats.


RESULTS
Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes.


CONCLUSIONS
The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.
Ooie
T
T
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita, Japan.
Takahashi
N
N
Saikawa
T
T
Nawata
T
T
Arikawa
M
M
Yamanaka
K
K
Hara
M
M
Shimada
T
T
Sakata
T
T
D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D018834:Chaperonin 60 / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006439:Hemodynamics; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism
D018834:Chaperonin 60; D004224:Diterpenes; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D013879:Thioredoxins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D003402:Creatine Kinase; C031049:geranylgeranylacetone