Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin

W. Tomisato, N. Takahashi, C. Komoto, K. Rokutan, T. Tsuchiya, T. Mizushima

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1674-1679
Number of pages6
JournalDigestive Diseases and Sciences
Volume45
Issue number8
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

geranylgeranylacetone
Indomethacin
Stomach
Guinea Pigs
Heat-Shock Proteins
Pharmaceutical Preparations
Protein Synthesis Inhibitors
Cytoprotection
Proteins
Anti-Inflammatory Agents
Ethanol

Keywords

  • Gastric mucosal cells
  • Geranylgeranylacetone
  • Heat-shock proteins
  • Indomethacin

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Tomisato, W., Takahashi, N., Komoto, C., Rokutan, K., Tsuchiya, T., & Mizushima, T. (2000). Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin. Digestive Diseases and Sciences, 45(8), 1674-1679. https://doi.org/10.1023/A:1005597902470

Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin. / Tomisato, W.; Takahashi, N.; Komoto, C.; Rokutan, K.; Tsuchiya, T.; Mizushima, T.

In: Digestive Diseases and Sciences, Vol. 45, No. 8, 2000, p. 1674-1679.

Research output: Contribution to journalArticle

Tomisato, W, Takahashi, N, Komoto, C, Rokutan, K, Tsuchiya, T & Mizushima, T 2000, 'Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin', Digestive Diseases and Sciences, vol. 45, no. 8, pp. 1674-1679. https://doi.org/10.1023/A:1005597902470
Tomisato, W. ; Takahashi, N. ; Komoto, C. ; Rokutan, K. ; Tsuchiya, T. ; Mizushima, T. / Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin. In: Digestive Diseases and Sciences. 2000 ; Vol. 45, No. 8. pp. 1674-1679.
@article{3ee063f85f6945ef9314c30b623b4147,
title = "Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from indomethacin",
abstract = "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.",
keywords = "Gastric mucosal cells, Geranylgeranylacetone, Heat-shock proteins, Indomethacin",
author = "W. Tomisato and N. Takahashi and C. Komoto and K. Rokutan and T. Tsuchiya and T. Mizushima",
year = "2000",
doi = "10.1023/A:1005597902470",
language = "English",
volume = "45",
pages = "1674--1679",
journal = "American Journal of Digestive Diseases",
issn = "0002-9211",
publisher = "Springer New York",
number = "8",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=0033827233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033827233&partnerID=8YFLogxK

U2 - 10.1023/A:1005597902470

DO - 10.1023/A:1005597902470

M3 - Article

C2 - 11007124

AN - SCOPUS:0033827233

VL - 45

SP - 1674

EP - 1679

JO - American Journal of Digestive Diseases

JF - American Journal of Digestive Diseases

SN - 0002-9211

IS - 8

ER -