TY - JOUR
T1 - Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin
AU - Tomisato, W.
AU - Takahashi, N.
AU - Komoto, C.
AU - Rokutan, K.
AU - Tsuchiya, T.
AU - Mizushima, T.
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan and the Mochida Memorial Foundation for Medical and Pharmaceutical Research.
PY - 2000
Y1 - 2000
N2 - One of the major side effects of nonsteroidal antiinflammatory drugs, such as indomethacin, is gastropathy. The purpose of this study was to search for a therapeutic drug to prevent this side effect in vitro. We found that geranylgeranylacetone, a unique antiulcer drug with a heat-shock protein-inducing ability, protected cultured guinea pig gastric mucosal cells from cell damage caused by indomethacin. This cytoprotective effect of geranylgeranylacetone required concentrations of more than 10-6 M and incubation periods of longer than 2 hr. Pretreatment of cells with an inhibitor of protein synthesis completely abolished the cytoprotective effect of geranylgeranylacetone, suggesting that some proteins induced by the drug are responsible for the cytoprotection. Since pretreatment of cells with low concentrations of ethanol, which also induced the heat-shock proteins, made cells resistant to indomethacin, heat-shock proteins are candidates for the proteins that are involved in the cytoprotective effect of geranylgeranylacetone against indomethacin.
AB - One of the major side effects of nonsteroidal antiinflammatory drugs, such as indomethacin, is gastropathy. The purpose of this study was to search for a therapeutic drug to prevent this side effect in vitro. We found that geranylgeranylacetone, a unique antiulcer drug with a heat-shock protein-inducing ability, protected cultured guinea pig gastric mucosal cells from cell damage caused by indomethacin. This cytoprotective effect of geranylgeranylacetone required concentrations of more than 10-6 M and incubation periods of longer than 2 hr. Pretreatment of cells with an inhibitor of protein synthesis completely abolished the cytoprotective effect of geranylgeranylacetone, suggesting that some proteins induced by the drug are responsible for the cytoprotection. Since pretreatment of cells with low concentrations of ethanol, which also induced the heat-shock proteins, made cells resistant to indomethacin, heat-shock proteins are candidates for the proteins that are involved in the cytoprotective effect of geranylgeranylacetone against indomethacin.
KW - Gastric mucosal cells
KW - Geranylgeranylacetone
KW - Heat-shock proteins
KW - Indomethacin
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U2 - 10.1023/A:1005597902470
DO - 10.1023/A:1005597902470
M3 - Article
C2 - 11007124
AN - SCOPUS:0033827233
SN - 0163-2116
VL - 45
SP - 1674
EP - 1679
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 8
ER -