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Hoshino, Tatsuya; Takano, Tatsunori; Tsutsumi, Shinji; Tomisato, Wataru; Tsuchiya, Tomofusa; Mizushima, Tohru

doi:10.1023/a:1020164000898

Cited by 19 publications

(12 citation statements)

References 34 publications

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“…In this experiment, cells were first incubated with PGE 2 (preincubation step) and then with ethanol in the presence of the same concentration of PGE 2 (incubation step). We confirmed that PGE 2 must be present in both steps in order to inhibit efficiently the ethanolinduced apoptosis (data not shown), as described previously (15). This method of PGE 2 treatment was thus used in all subsequent experiments.…”

Section: Methodssupporting

confidence: 88%

“…We also reported that PGE 2 suppressed the ethanolmediated activation of caspase-3 (15). We therefore examined here the effect of PGE 2 on the activation of various caspases, including caspase-3, where caspase activities were examined by the use of fluorogenic peptide substrates (Ac-DEVD-MCA (for caspase-3), Ac-IETD-MCA (for caspase-8), and Ac-LEHD-MCA (for caspase-9)).…”

Section: Effect Of Pgementioning

confidence: 99%

“…We also found that these gastric irritants induced apoptosis through a common pathway in which mitochondrial dysfunction plays an important role (13). In order to examine the direct cytoprotective effect of PGE 2 on gastric mucosal cells, we investigated previously the effect of PGE 2 on this gastric irritant-induced apoptosis in cultured guinea pig gastric mucosal cells, and we found that PGE 2 inhibited the apoptosis caused by various gastric irritants (ethanol, hydrogen peroxide, and hydrochloric acid) (15). The molecular mechanism governing this inhibitory effect of PGE 2 on apoptosis has, however, yet to be elucidated.…”

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confidence: 99%

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Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Hoshino

Tsutsumi

Tomisato

et al. 2003

Journal of Biological Chemistry

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135

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Prostaglandin E 2 (PGE 2 ) has a strong protective effect on the gastric mucosa in vivo; however, the molecular mechanism of a direct cytoprotective effect of PGE 2 on gastric mucosal cells has yet to be elucidated. Although we reported previously that PGE 2 inhibited gastric irritant-induced apoptotic DNA fragmentation in primary cultures of guinea pig gastric mucosal cells, we show here that PGE 2 inhibits the ethanol-dependent release of cytochrome c from mitochondria. Of the four main subtypes of PGE 2 receptors, we also demonstrated, using subtype-specific agonists, that EP 2 and EP 4 receptors are involved in the PGE 2 -mediated protection of gastric mucosal cells from ethanol-induced apoptosis. Activation of EP 2 and EP 4 receptors is coupled with an increase in cAMP, for which a cAMP analogue was found here to inhibit the ethanol-induced apoptosis. The increase in cAMP is known to activate both protein kinase A (PKA) and phosphatidylinositol 3-kinase pathways. An inhibitor of PKA but not of phosphatidylinositol 3-kinase blocked the PGE 2 -mediated protection of cells from ethanol-induced apoptosis, suggesting that a PKA pathway is mainly responsible for the PGE 2 -mediated inhibition of apoptosis. Based on these results, we considered that PGE 2 inhibited gastric irritant-induced apoptosis in gastric mucosal cells via induction of an increase in cAMP and activation of PKA, and that this effect was involved in the PGE 2 -mediated protection of the gastric mucosa from gastric irritants in vivo.

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Section: Methodssupporting

confidence: 88%

Section: Effect Of Pgementioning

confidence: 99%

mentioning

confidence: 99%

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Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Hoshino

Tsutsumi

Tomisato

et al. 2003

Journal of Biological Chemistry

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135

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“…In turn, PGs, and PGE 2 in particular, have cytoprotective effects on the gastric mucosa. 7,8,17,18) We previously reported that the primary culture of guinea pig gastric mucosal cells produced PGE 2 continuously even without stressors. 19) On this basis we considered whether or not the effect of indomethacin on hydrochloric acid-induced apoptosis such as that seen in Fig.…”

Section: )mentioning

confidence: 99%

“…2,3) We have also previously shown that endogenous factors that protect the gastric mucosa from such irritants (heat shock proteins (HSPs) and prostaglandins (PGs)) or anti-ulcer drugs suppress apoptosis and necrosis in this cell model. [4][5][6][7][8][9] This suggests that this in vitro system is useful for understanding the mechanisms underlying irritant-induced gastric lesions in vivo.…”

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confidence: 99%

Cytotoxic Synergy between Indomethacin and Hydrochloric Acid in Gastric Mucosal Cells

Tanaka

Tomisato

Tsutsumi

et al. 2004

Biological & Pharmaceutical Bulletin

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Orally ingested non-steroidal anti-inflammatory drugs (NSAIDs) and acid in gastric secretions are gastric irritants that co-exist at the surface of the gastric mucosa. Here, we examined the individual and combined effects of indomethacin, a typical NSAID, and hydrochloric acid on cell death in primary cultures of guinea pig gastric mucosal cells. Indomethacin alone (at concentrations less than 200 m mM) did not induce apoptosis; however, hydrochloric acid-induced apoptosis was stimulated in the presence of indomethacin (50-200 m mM). Isobologram analysis confirmed the presence of a cytotoxic synergy between indomethacin and hydrochloric acid. The synergistic response between the two gastric irritants was also observed for necrosis. Given that the IC 50 value of indomethacin for inhibition of prostaglandin synthesis is about 5 nM, the synergistic response between indomethacin and hydrochloric acid appears to be independent of the inhibition of cyclooxygenase activity by indomethacin.

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Profiling of Metabolites in a Fermented Soy Dietary Supplement Reinforces its Role in the Management of Intestinal Inflammation

Ethier,

Krishnamurthy,

Jeffrey

et al. 2024

Molecular Nutrition Food Res

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ScopeGastro‐AD (GAD) is a soy flour derived product that undergoes an industrial fermentation with Lactobacillus delbrueckii R0187 and has demonstrated clinical effects in gastroesophageal reflux and peptic ulcer symptom resolution. The aim of this study is to describe and link GAD's metabolomic profile to plausible mechanisms that manifest and explain the documented clinical outcomes.Methods and results1H NMR spectroscopy with multivariate statistical analysis is used to characterize the prefermented soy flour and GAD products. The acquired spectra are screened using various resources and the molecular assignments are confirmed using total correlation spectroscopy (TOCSY). Peaks corresponding to different metabolites are integrated and compared between the two products for relative changes. HPLC and GC are used to quantify some specific molecules. NMR analyses demonstrate significant changes in the composition of various assigned bioactive moieties. HPLC and GC analysis demonstrate deglycation of isoflavones after fermentation, resulting in estrogenically active secondary metabolites that have been previously shown to help to reduce inflammation.ConclusionThe identification of bioactive molecules, such as genistein and SCFAs, capable of modulating anti‐inflammatory signaling cascades in the stomach's gastric and neuroendocrine tissues can explain the reported biological effects in GAD and is supported by in vivo data.

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Cited by 19 publications

References 34 publications

Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Cytotoxic Synergy between Indomethacin and Hydrochloric Acid in Gastric Mucosal Cells

Profiling of Metabolites in a Fermented Soy Dietary Supplement Reinforces its Role in the Management of Intestinal Inflammation

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