Protective effects of heat shock protein 70 induced by geranylgeranylacetone on oxidative injury in rat intestinal epithelial cells.
OBJECTIVE
Geranylgeranylacetone (GGA), an anti-ulcer agent, has recently been demonstrated to protect a variety of cells and tissues via induction of heat shock protein (HSP)70 against numerous stresses. We investigated whether GGA induces HSP70 and protects against an oxidative stressor, monocrolamine (NH(2)Cl), in a rat intestinal epithelial cell line (IEC-18).


METHODS
IEC-18 cells pretreated with GGA (0.1-10 microM) were subjected to injury induced by NH(2)Cl. Cell viability was assessed, and endogenous HSP70 levels were determined by enzyme-linked immunosorbent assay in IEC-18 cells.


RESULTS
Treatment with GGA (0.1-10 microM) was found rapidly to elevate HSP70 levels and to protect against NH(2)Cl-induced injury in IEC-18 cells. Furthermore, quercetin, an inhibitor of HSP70 synthesis, diminished the protective effects of GGA in IEC-18 cells upon NH(2)Cl-caused injury.


CONCLUSIONS
The results of this study suggest that GGA plays an important role in defense mechanisms against oxidative injury in the intestine, primarily via induction of HSP70.
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tatsuya
T
Ohkawara
Hiroshi
H
Takeda
Morie
M
Nishiwaki
Jun
J
Nishihira
Masahiro
M
Asaka
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002700:Chloramines / Q000633:toxicity; D004224:Diterpenes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
D000897:Anti-Ulcer Agents; D002700:Chloramines; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; C030816:chloramine; C031049:geranylgeranylacetone