• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.389-399
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• 2015

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc ($Zn^{2+}$) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of $Zn^{2+}$ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular $Zn^{2+}$ levels are largely regulated by metallothioneins (MTs), $Zn^{2+}$ importers (ZIPs), and $Zn^{2+}$ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of $Zn^{2+}$. However, these regulatory actions of $Zn^{2+}$ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular $Zn^{2+}$ levels, $Zn^{2+}$-mediated signal transduction, impacts of $Zn^{2+}$ on ion channels and mitochondrial metabolism, and finally, the implications of $Zn^{2+}$ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of $Zn^{2+}$.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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• pp.223-228
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• 2013

The calcium-activated $K^+$ ($BK_{Ca}$) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. $Ca^{2+}$ is the main regulator of $BK_{Ca}$ channel activation. The $BK_{Ca}$ channel contains two high affinity $Ca^{2+}$ binding sites, namely, regulators of $K^+$ conductance, RCK1 and the $Ca^{2+}$ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular $Ca^{2+}$ levels through diverse G proteins such as $G{\alpha}_{q/11}$, $G{\alpha}_i$, $G{\alpha}_{12/13}$, and $G{\alpha}s$ and the related signal transduction pathway. In the present study, we examined LPA effects on $BK_{Ca}$ channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated $BK_{Ca}$ channel activation was also attenuated by the PLC inhibitor U-73122, $IP_3$ inhibitor 2-APB, $Ca^{2+}$ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated $BK_{Ca}$ channel activation. The present study indicates that LPA-mediated activation of the $BK_{Ca}$ channel is achieved through the PLC, $IP_3$, $Ca^{2+}$, and PKC pathway and that LPA-mediated activation of the $BK_{Ca}$ channel could be one of the biological effects of LPA in the nervous and vascular systems.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.257-270
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• 1986

It has been reported that the luteal function may be regulated by the intracellular calcium in luteal cells (Higuchi et al, 1976; Dorflinger et at, 1984; Gore and Behrman, 1984) which is adjusted partially by $Ca^{++}-ATPase$ activities in luteal cell membranes (Verma and Pennistion, 1981). However, the physicochemical and kinetic properties of $Ca^{++}-ATPase$ in luteal membranes were not fully characterized. This study was, therefore, undertaken to partially characterize the physicochemical and kinetic properties of $Ca^{++}-ATPase$ system in luteal membranes and microsomal fractions, known as an one of the major $Ca^{++}$ storge sites (Moore and Pastan, 1978), from the highly luteinized ovary Highly luteinized ovaries were obtained from PMSG-hCG injected immautre female rats. Light membrane and heavy membrane fractions and microsomal fractions were prepared by the differential and discontinuous sucrose density gradient centrifugation method desribed by Bramley and Ryan (1980). Light membrane and heavy membrane fractions and microsomal fractions from highly luteinized ovaries are composed of the two different kinds of $Ca^{++}-ATPase$ system. One is the high affinity $Ca^{++}-ATPase$ which is activated in low $Ca^{++}$ concentration (Km, 10-30 nM), the other is low affinity $Ca^{++}-ATPase$ activated in higher $Ca^{++}$ concentration $(K_{1/2},\;40\;{\mu}M)$. At certain $Ca^{++}$ concentrations, activities of high and low affinity $Ca^{++}-ATPase$ are the highest in light membrane fractions and are the lowest in microsomal fractions. It appeares that high affinity $Ca^{++}-ATPase$ system have 2 binding sites for ATP (Hill's coefficient; around 2 in all membrane fractions measured) and the positive cooperativity of ATP bindings obviously existed in each membrane fractions. The optimum pH for high affinity $Ca^{++}-ATPase$ activation is around S in all membrane fractions measured. The lipid phase transition temperature measured by Arrhenius plots of high affinity $Ca^{++}-ATPase$ activity is around $25^{\circ}C$. The activation energies of high affinity $Ca^{++}-ATPase$ below the transition temperature are similar in each membrane fractions, but at the above transition temperature, it is the hightest in heavy membrane fractions and the lowest in microsomal fractions. According to the above results, it is suggested that intracellular $Ca^{++}$ level, which may regulate the luteal function, may be adjusted primarily by the high affinity $Ca^{++}-ATPase$ system activated in intracellular $Ca^{++}$ concentration range $(below\;0.1\;{\mu}M)$.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.868-873
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might playa role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside $Rg_{2-}$, CK-, or M4-induced regulation of $\alpha3\beta4$ nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ($I_{Ach}$) in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor. Co-treatment of ginsenoside $Rg_2$, CK, or M4 with ACh inhibited IAch in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and co-treatment of ginsenoside $Rg_2$ or M4 but not CK with ACh inhibited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1394-1398
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• 2006

Functionalities of drum-dried fish muscle protein from pH shifting process have been investigated by determining solubility, emulsion activity, rehydration, fat-adsorption capacity, viscosity, and color. Solubility was higher in recovered protein at pH 7.0 than that at pH 5.5, and not dependent on ionic strength. Solubility of the dried protein recovered at pH 7.0 depended on pH of solvent, and lowest in the range of pH 3 to pH 6. The dried protein showed relatively low emulsion capacity in all the samples. Emulsion stability, foam capacity and foam stability were not observed in the samples. Viscosity was in the range of $50,200\sim39,000cP$. Rehydration and fat-binding capacities were $2.63\sim2.89g$-water/g and $2.13\sim2.17g$-oil/g, respectively, and not dependent on particle size and pH. Drum-dried fish muscle protein has a potential application as an ingredient of meat patty products.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.230-236
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• 2007

This study was conducted to investigate the contents of the total phenolic compounds, and DPPH, ABTS radical scavenging activities of phenolic acid fractions of ginseng according to steaming times. Also the individual phenolic acid compositions and contents were analyzed by GC. The contents of the total phenolic compounds proportionally increased from 0.530 to 2.893% according to steaming times. Phenolic acid fractions were separated according to bound types, and the insoluble bound form fraction showed the highest contents followed by ester form fraction and free form fraction. The total contents of these three fractions (1.031-1.416%) were not significantly influenced by steaming times. Salicylic, cinamic, p-hydroxybenzoic, gentisic, vanillic, syringic, caffeic, ferolic acid were found in each fraction, and gentisic and ferolic acid were the major phenolic acid. Each phenolic acid fraction showed over 50% of DPPH and ABTS radical scavenging activities. There were no differences between the phenolic acid fractions according to binding types. Free radical scavenging activities were affected by a number of steaming times and augmented as steaming times increased.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.23-30
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• 2017

Background: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. Methods: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Results: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the $C/EBP{\beta}$ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase $3{\beta}$, which are also essential for stimulating the expression of $CEBP{\beta}$. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. Conclusion: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

• Journal of Life Science
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• v.22 no.9
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• pp.1194-1200
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• 2012

Lactic acid bacteria are generally recognized as beneficial probiotic organisms. Recent studies revealed that the potential of probiotic strains was essentially dependent on the bacterial-binding and adhesion capabilities to gut epithelial cells and the hydrophobicity of the cell surface. In this study, we screened some indigenous lactic acid bacteria from Kimchi and selected one lactic acid bacterium as a potential probiotic based on its cell surface hydrophobicity. Analysis of the 16S rRNA gene sequences of probiotic isolates indicated that the selected isolate (BCNU 9070 strain) was a member of Pediococcus pentosaceus. P. pentosaceus BCNU 9070 showed resistance to bile acids and acidic pH. The P. pentosaceus BCNU 9070 strain also inhibited the cell growth of six food-borne pathogens including Listeria monocytogenes and Shigella sonnei. In addition, the P. pentosaceus BCNU 9070 strain expressed bile salt hydrolase activity and showed an ability to assimilate cholesterol in vitro. On the basis of these results, P. pentosaceus BCNU 9070 is considered to have probiotic potential for applications in functional foodstuffs.

• Journal of Life Science
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• v.22 no.12
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• pp.1600-1607
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• 2012

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

• Microbiology and Biotechnology Letters
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• v.31 no.4
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• pp.368-376
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• 2003

Cyclodextrin glucanotransferase (CGTase) from Paenibacillus sp. JB-13 was immobilized on various carriers by several immobilization methods such as ionic binding, covalent linkage and ultrafiltration to improve the process performance. The ultrafiltration and covalent linkage with CNBr-activated sepharose 4B were found as the best method for immobilization of CGTase. The ability of CGTase immobilization onto CNBr-activated sepharose 4B was as high as 18,000 units/g resin when the conditions was as follows: contact time 9 hrs at $37^{\circ}C$, pH 6.0, 100 nm and enzyme loading 24,000 units/g resin. The optimum conditions for production of 2-O-$\alpha$-D-Glucopyranosyl L-Ascorbic acid by immobilized CGTase turned out to be: pH 5.0, temperature $37^{\circ}C$, 20% substrate solution containing 8% (w/v) of soluble starch and 12% (w/v) of L-ascorbic acid sodium salt, 100 rpm, far 25 hrs and with 800 units of immobilized CGTase/ml substrate solution. Moreover the CGTase activity could be stably maintained for 8 times of repetitive reactions after removing products by ultrafiltration through YM 10 membrane.