Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors

Manabu Nakashita, Hidekazu Suzuki, Soichiro Miura, Takao Taki, Keita Uehara, Tohru Mizushima, Hiroshi Nagata, Toshifumi Hibi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. Methods: The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. Results: Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. Conclusion: The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.

Original languageEnglish
Pages (from-to)354-362
Number of pages9
JournalDigestive Diseases and Sciences
Volume58
Issue number2
DOIs
Publication statusPublished - 2013 Feb

Fingerprint

ceramide glucosyltransferase
Ceramides
Stomach Ulcer
Acetic Acid
Stomach
Apoptosis
Ulcer

Keywords

  • Acetic acid
  • Apoptosis
  • Ceramide
  • Gastric ulcer
  • Glucosylceramide inhibitor

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors. / Nakashita, Manabu; Suzuki, Hidekazu; Miura, Soichiro; Taki, Takao; Uehara, Keita; Mizushima, Tohru; Nagata, Hiroshi; Hibi, Toshifumi.

In: Digestive Diseases and Sciences, Vol. 58, No. 2, 02.2013, p. 354-362.

Research output: Contribution to journalArticle

Nakashita, M, Suzuki, H, Miura, S, Taki, T, Uehara, K, Mizushima, T, Nagata, H & Hibi, T 2013, 'Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors', Digestive Diseases and Sciences, vol. 58, no. 2, pp. 354-362. https://doi.org/10.1007/s10620-012-2350-x
Nakashita, Manabu ; Suzuki, Hidekazu ; Miura, Soichiro ; Taki, Takao ; Uehara, Keita ; Mizushima, Tohru ; Nagata, Hiroshi ; Hibi, Toshifumi. / Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors. In: Digestive Diseases and Sciences. 2013 ; Vol. 58, No. 2. pp. 354-362.
@article{055961dcd77d42ff8a2b1b13d189d1b1,
title = "Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors",
abstract = "Introduction: Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. Methods: The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. Results: Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. Conclusion: The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.",
keywords = "Acetic acid, Apoptosis, Ceramide, Gastric ulcer, Glucosylceramide inhibitor",
author = "Manabu Nakashita and Hidekazu Suzuki and Soichiro Miura and Takao Taki and Keita Uehara and Tohru Mizushima and Hiroshi Nagata and Toshifumi Hibi",
year = "2013",
month = "2",
doi = "10.1007/s10620-012-2350-x",
language = "English",
volume = "58",
pages = "354--362",
journal = "American Journal of Digestive Diseases",
issn = "0002-9211",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors

AU - Nakashita, Manabu

AU - Suzuki, Hidekazu

AU - Miura, Soichiro

AU - Taki, Takao

AU - Uehara, Keita

AU - Mizushima, Tohru

AU - Nagata, Hiroshi

AU - Hibi, Toshifumi

PY - 2013/2

Y1 - 2013/2

N2 - Introduction: Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. Methods: The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. Results: Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. Conclusion: The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.

AB - Introduction: Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. Methods: The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. Results: Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. Conclusion: The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.

KW - Acetic acid

KW - Apoptosis

KW - Ceramide

KW - Gastric ulcer

KW - Glucosylceramide inhibitor

UR - http://www.scopus.com/inward/record.url?scp=84876312596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876312596&partnerID=8YFLogxK

U2 - 10.1007/s10620-012-2350-x

DO - 10.1007/s10620-012-2350-x

M3 - Article

C2 - 22918683

AN - SCOPUS:84876312596

VL - 58

SP - 354

EP - 362

JO - American Journal of Digestive Diseases

JF - American Journal of Digestive Diseases

SN - 0002-9211

IS - 2

ER -