• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.245-252
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• 1993

Amiloride is a potassium sparing duretic which specifically inhibits $Na{^+}$ channels. In the present study, we investigated the possible interaction of amiloride with $A_1$ adenosine receptors-adenylyl cyclase system in crude adipocytic plasma membrane fractions prepared from Sprague-Dawley rats. When the function of $G_i$ protein (inhibitory guanine nucleotide binding protein) was assessed by determining the effects of GTP on isoproterenol-stimulated adenylyl cyclase activity, the inhibitory effect of high concentrations of GTP was not observed in the presence of amiloride. In contrast, the adenosine receptor-mediated inhibition of the enzyme activity, as determined empolying 2-chloroadenosine, was either unchanged or even more enhanced by amiloride depending on the concentrations of 2-chloroadenosine. Thus, it appears that GTP- and receptor-mediated inhibitory function of $G_{i}$ proteins can be separated from one another. Receptor-mediated function of $G_{s}$ protein did not appear to be significantly affected by amiloride, since the inhibition of isoproterenol-stimulated adenylyl cyclase activity by propranolol under the same conditions was not significantly altered by amiloride. The enhancement of 2-chloroadenosine-mediated inhibition of adenylyl cyclase by amiloride was maintained in the presence of 150 mM NaCl. In summary, these results suggest that amiloride interacts both with $A_{l}$ adenosine receptors and with $G_i$ proteins in adipocytic membranes. Its binding to the $A_1$ adenosine receptors appears to facilitate the coupling of the receptors with $G_i$ proteins thereby enhancing the inhibition of isoproterenol-stimulated adenylyl cyclase activity by $A_1$ adenosine agonist, and the direct interaction with $G_i$ proteins appears to remove the GTP-dependent inhibitory effect on adenylyl cyclase activity.

• IMMUNE NETWORK
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• v.4 no.2
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• pp.100-107
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• 2004

Background: The fruit of Rubus coreanus (RC), a perennial herb, has been cultivated for a long time as a popular vegetable. The anti-allergy mechanism of RC is unknown. The purpose of this study is to investigate the inhibitory effect of RC on compound 48/80- or anti-DNP IgE-induced mast cell activation. Methods: For this, influences of RC on the compound 48/80-induced degranulation, histamine release, calcium influx and the change of the intracellular cAMP (cyclic adenosine-3',5' monophosphate) levels of rat peritoneal mast cells (RPMC) and on the anti-DNP IgE-induced histamine release of RPMC were observed. Results: The pretreatment of RC inhibited compound 48/80-induced degranulation, histamine release and intracelluar calcium uptake of RPMC. The anti-DNP IgE-induced histamine release of RPMC was significantly inhibited by pretreatment of RC. The RC increased the level of intracellular cAMP of RPMC, and the pretreatment of RC inhibited compound 48/80-induced decrement of intracellular cAMP of RPMC. Conclusion: These results suggest that RC contains some substances with an activity to inhibit the compound 48/80- or anti-DNP IgE-induced mast cell activitation. The inhibitory effects of RC are likely due to the stabilization of mast cells by blocking the calcium uptake and enhancing the level of intracellular cAMP.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.5
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• pp.496-501
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• 1992

The present work tested the inhibitory effects of bile acids on the cholesterol biosynthesis and the activity of HMG-CoA reductase in cultured rat hepatocytes. The uptake of bile acids in hepatocytes were increased in according to the different bile acid concentrations and culture times. The rate of cholesterol synthesis in cells were inversely decreased to the bile acid concentrations and culture times. As expected, insulin injection (4 units/100g body weight) showed an enhancing effect of the cholesterol synthesis and the HMG-CoA reductase activity. The addition of bile acids in medium of insulin-treated hepatocytes also showed the suppressing effect. This effect was directly confirmed in isolated hepatic icrosomes by the test of HMG-CoA reductase activity. In the test of $Na^+$,$K^+$-ATPase activity in the isolated hepatocyte membrane, only the cholic acid did not stimulate the enzyme system. The reason of such difference is not obvious, but this result indicates that the cholic acid could be absorbed by simple diffusion.

• Mycobiology
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• v.50 no.5
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• pp.269-293
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• 2022

Oomycete pathogens that belong to the genus Phytophthora cause devastating diseases in solanaceous crops such as pepper, potato, and tobacco, resulting in crop production losses worldwide. Although the application of fungicides efficiently controls these diseases, it has been shown to trigger negative side effects such as environmental pollution, phytotoxicity, and fungicide resistance in plant pathogens. Therefore, biological control of Phytophthora-induced diseases was proposed as an environmentally sound alternative to conventional chemical control. In this review, progress on biological control of the soilborne oomycete plant pathogens, Phytophthora capsici, Phytophthora infestans, and Phytophthora nicotianae, infecting pepper, potato, and tobacco is described. Bacterial (e.g., Acinetobacter, Bacillus, Chryseobacterium, Paenibacillus, Pseudomonas, and Streptomyces) and fungal (e.g., Trichoderma and arbuscular mycorrhizal fungi) agents, and yeasts (e.g., Aureobasidium, Curvibasidium, and Metschnikowia) have been reported as successful biocontrol agents of Phytophthora pathogens. These microorganisms antagonize Phytophthora spp. via antimicrobial compounds with inhibitory activities against mycelial growth, sporulation, and zoospore germination. They also trigger plant immunity-inducing systemic resistance via several pathways, resulting in enhanced defense responses in their hosts. Along with plant protection, some of the microorganisms promote plant growth, thereby enhancing their beneficial relations with host plants. Although the beneficial effects of the biocontrol microorganisms are acceptable, single applications of antagonistic microorganisms tend to lack consistent efficacy compared with chemical analogues. Therefore, strategies to improve the biocontrol performance of these prominent antagonists are also discussed in this review.

• Journal of the Korean Chemical Society
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• v.54 no.1
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• pp.65-70
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• 2010

We describe the immune stimulatory effects of compounds determined by means of activity-monitored extraction and isolation techniques. As a result, 4-carboethoxy-6-methoxy-2-quinolone (1) and 4-carboethoxy-6-hydroxy-2-quinolone (2) were isolated from the ethyl acetate-soluble fraction of the Oryza sativa cv. Heugnambyeo bran, and were determined to exert significant inhibitory effects in macrophage cell line (murine RAW 264.7) and murine splenocytes. The structures were elucidated on the basis of spectroscopic evidence, particularly the results obtained via hetero nuclear multiple-bond connectivity and high-resolution MS spectroscopy. Up to date, compound (1) was isolated as natural sources for the first time.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.411-417
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• 1998

The role of phospholipase ($A_2\;PLA_2$) in tumor cell growth was investigated using SK-N-MC human neuroblastoma cells. 4-Bromophenacyl bromide (BPB) and mepacrine (Mep), known $PLA_2$ inhibitors, suppressed growth of the tumor cells in a dose-dependent manner without a significant cytotoxicity. Melittin (Mel), a $PLA_2$ activator, enhanced the cell growth in a concentration-dependent fashion. The growth-enhancing effects of Mel were significantly reversed by the co-treatment with $PLA_2$ inhibitors. In addition, Mel induced intracellular $Ca^{2+}$ release from internal stores like as did serum, a known intracellular $Ca^{2+}$ agonist in the tumor cells. Intracellular $Ca^{2+}$ release induced by these agonists was significantly blocked by $PLA_2$ inhibitors at growth-inhibitory concentrations. Arachidonic acid (AA), a product of the $PLA_2-catalyzed$ reaction, induced cell growth enhancement and intracellular $Ca^{2+}$ release. These effects of AA were significantly blocked by BAPTA/AM, an intracellular $Ca^{2+}$ chelator. Taken together, these results suggest that the modulation of $PLA_2$ activity may be one of the regulatory mechanisms of cell growth in human neuroblastoma cells. Intracellular $Ca^{2+}$ may act as a key mediator in the $PLA_2-induced$ growth regulation.

• Korean Journal of Environmental Biology
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• v.21 no.3
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• pp.308-312
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• 2003

Various pesticides known or suspected to interfere with steroid hormone function were screened toy effects in leydig cells on catalytic activity and mRNA expression of aromatase. Dichlorodiphenyltrichloroethane (DDT) is a widespread environmental pollutant. In this study, we investigated the effect of DDT on testosterone production through aromatase activity and its molecular mechanism in testicular leydig cell, R2C by using radioimmunoassay (RIA). As the results, the potent leydig: cell activator LH increased testosterone production compared to the control. DDT exposure significantly decreased testosterone production in R2C cell. In addition, DDT was found to increase aromatase gene expression and activity in R2C cell in a dose dependent manner. In order to assess whether the suppressive effects of DDT on LH-inducible testosterone (T) production might be influenced by the ER, ICI 182.780 was used, and it was found that these inhibitory effects of DDT were antagonized by ICI 182.780, implying that the estrogen receptor (ER) mediates the suppressive effects of DDT. Furthermore, the inducible effects of DDT on aromatase gene expression might be influenced by the ER, ICI 182.780 was used, and it was found that these enhancing effects of DDT were antagonized by ICI 182.780, implying that the ER mediates the inducible effects of DDT. Our results indicated that DDT inhibition of luteinizing hormone (LH) -inducible T production in R2C cell is mediated through aromatase. However, the precise mechanisms by which DDT enhance in R2C cell remains unknown. The current study suggests the possibility that DDT might act as a modulator aromatase gene transcription.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1234-1244
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• 2022

Oral streptococci are considered as an opportunistic pathogen associated with initiation and progression of various oral diseases. However, since the currently-available treatments often accompany adverse effects, alternative strategy is demanded to control streptococci. In the current study, we investigated whether short-chain fatty acids (SCFAs), including sodium acetate (NaA), sodium propionate (NaP), and sodium butyrate (NaB), can inhibit the growth of oral streptococci. Among the tested SCFAs, NaP most potently inhibited the growth of laboratory and clinically isolated strains of Streptococcus gordonii under anaerobic culture conditions. However, the growth inhibitory effect of NaP on six different species of other oral streptococci was different depending on their culture conditions. Metabolic changes such as alteration of methionine biosynthesis can affect bacterial growth. Indeed, NaP enhanced intracellular methionine levels of oral streptococci as well as the mRNA expression level of methionine biosynthesis-related genes. Collectively, these results suggest that NaP has an inhibitory effect on the growth of oral streptococci, which might be due to alteration of methionine biosynthesis. Thus, NaP can be used an effective bacteriostatic agent for the prevention of oral infectious diseases caused by oral streptococci.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2973-2978
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• 2013

Maesil (Prunus mume Siebold & Zucc.), a member of the genus Rosaceae, has been reported to have antioxidative effects, as well as anticancer influence in many cancer lines. Thus, this present study was designed to investigate the inhibitory effect of fermented Maesil with probiotics against 7,12-dimethylbenz[a]anthracene (DMBA), 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced mouse skin carcinogenesis via its antioxidative potential. Mice were fed a diet containing fermented Maesil, containing either 1% (1% FM fed group) or 2% (2% FM fed group) along with probiotics following DMBA and TPA exposure. Continuous ingestion of the experimental feed markedly inhibited skin carcinogenesis, as evidenced by a marked decrease in papilloma numbers and epidermal hyperplasia as well as cellular proliferation and the percentage of proliferating-cell nuclear antigen positive cells. Also, the FM fed group showed an increase of total antioxidant capacity as well as an increased level of phase II detoxifying enzymes such as superoxide dismutase, concurrent with a decreased lipid peroxidation activity level. Taken together, these results suggest that fermented Maesil has the ability to suppress the development of DMBA-TPA induced skin carcinogenesis, via the reduction of lipid peroxidation, enhancing total antioxidant capacity and phase II detoxifying enzyme.