• Journal of Food Hygiene and Safety
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• v.19 no.3
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• pp.161-166
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• 2004

We investigated the antiplatelet effect of a newly synthesized guanidine derivative KR-32558, a sodium-hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mechanisms of action. KR-32558 concentration -dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 ${\mu}g/ml$) with an $IC_{50}$ value of 85.9 ${\mu}M$, but with much weaker potency against aggregation induced by thapsigargin (0.5 ${\mu}M$) or A23187 (5 ${\mu}M$). And had no effect on platelet aggregation induced by arachidonic acid (100 ${\mu}M$), thrombin (0.05 U/ml) and U46619 (1 ${\mu}M$) up to 100 ${\mu}M$. KR-32558 completely inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at concentration of 100${\mu}iM$. Taken together, these observation suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.

• Nuclear Engineering and Technology
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• v.56 no.3
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• pp.893-899
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• 2024

In a secondary cooling system of a sodium-cooled fast reactor (SFR), rapid detection of hydrogen due to sodium-water reaction (SWR) caused by water leakage from a heat exchanger tube of a steam generator (SG) is important in terms of safety and property protection of the SFR. For hydrogen detection, the hydrogen detectors using atomic transmission phenomenon of hydrogen within Ni-membrane were used in Japanese proto-type SFR "Monju". However, during the plant operation, detection signals of water leakage were observed even in the situation without SWR concerning temperature up and down in the cooling system. For this reason, the study of a new hydrogen detector has been carried out to improve stability, accuracy and reliability. In this research, the authors focus on the difference in composition of hydrogen and the difference between the background hydrogen under normal plant operation and the one generated by SWR and theoretically estimate the hydrogen behavior in liquid sodium by using ultra-accelerated quantum chemical molecular dynamics (UA-QCMD). Based on the estimation, dissolved H or NaH, rather than molecular hydrogen (H₂), is the predominant form of the background hydrogen in liquid sodium in terms of energetical stability. On the other hand, it was found that hydrogen molecules produced by the sodium-water reaction can exist stably as a form of a fine bubble concerning some confinement mechanism such as a NaH layer on their surface. At the same time, we observed experimentally that the fine H₂ bubbles exist stably in the liquid sodium, longer than previously expected. This paper describes the comparison between the theoretical estimation and experimental results based on hydrogen form in sodium in the development of the new hydrogen detector in Japan.

• BMB Reports
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• v.47 no.7
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• pp.393-398
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• 2014

The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic stimuli has been studied; however, as little is known about its role in death receptor-mediated cell death, this study was designed to investigate the effect of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080 adenocarcinoma cells were cultured in high concentration of glucose media and transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1 cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1 oligomerization, mitochondrial $Ca^{2+}$ accumulation, and significant inhibition of sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE significantly increased cell death, which suggests that the viability of BI-1 cells is affected by the maintenance of intracellular pH homeostasis through NHE.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.20-25
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• 2005

The present study was performed to evaluate antiarrhythmic effects of KR-32570, a novel inhibitor of sodium hydrogen exchanger subtype-1 (NHE-1), in rat arrhythmia induced by focal ischemia and reperfusion. During ischemia, KR-32570 significantly decreased the number of premature ventricular contraction (PVC) from 152.0 times to 75.5, 52.4 and 20.0 times for 0.1, 0.3 and 1.0 mg/kg, respectively (p<0.05) and the duration of ventricular tachycardia (VT) from 88.1 s to 35.8, 7.7 and 1.3 s, respectively(p<0.05) in anesthetized rats subjected to 10-min coronary occlusion of coronary artery. Similarlt to ischemia-induced arrhythmia, KR-32570 significantly decreased reperfusion-induced arrhythmia including PVC (41.3, 21.5, 11.3 and 6.6 times at vehicle, 0.1, 0.3 and 1.0 mg/kg, respectively, p<0.05) and VT (100.5, 64.2, 25.8 and 25.2 s, respectively, p<0.05), and VF (86.9, 27.5, 6.9 and 0 s, respectively, p<0.05). Moreover, KR-32570 dose-dependently decreased the incidence of mortality occurring after reperfusion (41, 27, 18 and 0% at vehicle, 0.1, 0.3, 1.0 mg/kg, respectively). These results suggest that KR-32570 has a potent antiarrhythmic effect in rat arrhythmia induced by ischemia and reperfusion.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2004.05a
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• pp.231-231
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• 2004

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2621-2625
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• 2009

To identify a non-acylguanidine NHE-1 inhibitor, an acylguanidne group was replaced with an imidazole group in the potent NHE-1 inhibitors with furan or benzothiphene core template, found from our previous studies. We synthesized and biologically evaluated 4-heteroaryl-2-amino-5-methylimidazole derivatives. All those imidazole compounds (16-18) represented the potent NHE-1 inhibitory activities, similar to the corresponding acylguanidine compounds.

• Animal Bioscience
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• v.34 no.5
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• pp.880-885
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• 2021

Objective: Omasum is an important site for the absorption of short chain fatty acids. The major route for the transport of acetate is via sodium hydrogen exchanger (NHE). However, a discrepancy in the symmetry of sodium and acetate transport has been previously reported, the mechanism of which is unclear. In this study, we investigated the possible role of carbonic anhydrase (CA) for this asymmetry. Methods: Omasal tissues were isolated from healthy sheep (N = 3) and divided into four groups; pH 7.4 and 6.4 alone and in combination with Ethoxzolamide. Electrophysiological measurements were made using Ussing chamber and the electrical measurements were made using computer controlled voltage clamp apparatus. Effect(s) of CA inhibitor on acetate and sodium transport flux rate of Na22 and 14C-acetate was measured in three different flux time periods. Data were presented as mean±standard deviation and level of significance was ascertained at p≤0.05. Results: Mucosal to serosal flux of Na (JmsNa) was greater than mucosal to serosal flux of acetate (JmsAc) when the pH was decreased from 7.4 to 6.4. However, the addition of CA inhibitor almost completely abolished this discrepancy (JmsNa ≈ JmsAc). Conclusion: The results of the present study suggest that the additional protons required to drive the NHE were provided by the CA enzyme in the isolated omasal epithelium. The findings of this study also suggest that the functions of CA may be exploited for better absorption in omasum.

• Parasites, Hosts and Diseases
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• v.54 no.1
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• pp.21-29
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• 2016

The sodium hydrogen exchanger 1 (NHE1), which functions in maintaining the ratio of $Na^+$ and $H^+$ ions, is widely distributed in cell plasma membranes. It plays a prominent role in pH balancing, cell proliferation, differentiation, adhesion, and migration. However, its exact subcellular location and biological functions in Toxoplasma gondii are largely unclear. In this study, we cloned the C-terminal sequence of T. gondii NHE1 (TgNHE1) incorporating the C-terminal peptide of NHE1 (C-NHE1) into the pGEX4T-1 expression plasmid. The peptide sequence was predicted to have good antigenicity based on the information obtained from an immune epitope database. After induction of heterologous gene expression with isopropyl-b-D-thiogalactoside, the recombinant C-NHE1 protein successfully expressed in a soluble form was purified by glutathione sepharose beads as an immunogen for production of a rabbit polyclonal antiserum. The specificity of this antiserum was confirmed by western blotting and immunofluorescence. The antiserum could reduce T. gondii invasion into host cells, indicated by the decreased TgNHE1 expression in T. gondii parasites that were pre-incubated with antiserum in the process of cell entry. Furthermore, the antiserum reduced the virulence of T. gondii parasites to host cells in vitro, possibly by blocking the release of $Ca^{2+}$. In this regard, this antiserum has potential to be a valuable tool for further studies of TgNHE1.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.91-95
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• 2012

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of $NH_4Cl$ for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 $Na^+/H^+$ exchanger (NHE3), type 1 $Na^+/{HCO_3}^-$ cotransporter (NBC1), Na-$K^+$ ATPase, $H^+$-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, $H^+$-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, $H^+$-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, $H^+$-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

• KSBB Journal
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• v.11 no.5
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• pp.606-612
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• 1996

A specific ammino auid in a mixture can be crystallized inside an ion exchange column when displacer concentration is high enough to concentrate the amino acid in a pure band beyond its solubility limit. Glutamic acid formpd a discrete crystal layer in a cation exchanger column by operating displacement development mode and using a high concentration of displacer NaOH. The glutamic acid crystal formed was eluded from the column with the effluent stream and collected in a fraction collector. When 1.0 M of NaOH was used as a displacer, more than 60% of the loaded glutamic acid was recovered as crystal. The continuous crystallization and dissolution of crystal occurred, resulting in apparent movement of the crystal along the column without clogging or pressure increase. NaOH was proved a better displacer than NaCl because hydroxide ions neutralized hydrogen ions released from the resin and thus reduced the number of hydrogen ion competing with sodium ion for re-adsorption. The displacement development process coupled with crystallization provided higher concentration and recovery of glutamic acrid than conventional chromatography.