Eui-Bae Jeung

Chungbuk National University, Chinsen, Chungcheongbuk-do, South Korea

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Publications (178)489.99 Total impact

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    ABSTRACT: Chamaecyparis obtusa has been traditionally used as an antibiotic agent and in cosmetics for the prevention of microorganism infection and skin troubles. Atopic dermatitis (AD) is a chronic inflammatory skin disease that encompasses immunologic responses, susceptibility factors and compromised skin-barrier function. Use of plant medicines in therapeutic treatment of AD has recently been suggested as an alternative therapeutic option. The present study examined the effect of elemol, an active component of Chamaecyparis obtusa, on AD using in vivo and in vitro models. RBL-2H3 cells were stimulated with concanavalin A and dinitrophenyl human serum albumin, and atopic dermatitis was induced in BALB/c mice by topical application of 2,4-dinitrochlorobenzene (DNCB) prior to elemol treatment. The mRNA expression was evaluated by reverse transcription quantitative polymerase chain reaction, and the levels of β-hexosaminidase and serum immunoglobulin E (IgE) were examined by ELISA. Histological changes were also performed by microscopy. Elemol attenuated the onset of AD-like skin lesions, reduced serum IgE levels and decreased mast cell infiltration into the dermis and hypodermis. In addition, elemol downregulated the transcriptional expression of several pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IκBα, in the skin of the DNCB‑induced animal models of AD. In the RBL-2H3 mast cell line, elemol significantly inhibited the mRNA expression of IL-4 and IL-13, and further attenuated the release of β-hexosaminidase from mast cells. Histological examination revealed that elemol significantly ameliorated the DNCB-induced dermal destruction in mice. The results of the present study suggested that elemol may have therapeutic potential in the treatment of AD due to its immunosuppressive effects.
    International Journal of Molecular Medicine 05/2015; DOI:10.3892/ijmm.2015.2228 · 1.88 Impact Factor
  • Changhwan Ahn, Beum-Soo An, Eui-Bae Jeung
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    ABSTRACT: Calcium homeostasis refers to the regulation of calcium ion concentration in the body. This concentration is tightly controlled by a stabilizing system consisting of calcium channels and calcium buffering proteins. Calcium homeostasis is crucial for cell survival. Various forms of cell death (e.g., necrosis and apoptosis) also share calcium signaling pathways and molecular effectors. Calcium acts as not only a ubiquitous second messenger involved in apoptosis along with various cell death inducers but also a regulator for the synthesis of enzymes/hormones such as insulin. We hypothesized that streptozotocin disrupts calcium homeostasis and the altered intracellular calcium levels may induce cell death. After streptozotocin administration, blood glucose level was increased while insulin levels decreased. The expression of insulin response markers also decreased relative to the vehicle group. L-type voltage-gated calcium channels expression and sarcoplasmic reticulum Ca(2+) ATPase were increased by streptozotocin. Calcium buffering protein calbindin-D9k and calmodulin family members were also increased. The expression of genes involved in transporting calcium ions to the endoplasmic reticulum (ER) was decrease while the expression of those affecting the removal of calcium from the ER was increased. Depletion of calcium from the ER leads to ER-stress and can induce apoptosis. In the streptozotocin-treatment group, apoptosis markers were increased. Taken together, these results imply that the disruption of calcium homeostasis by streptozotocin induces ER-stress and leads to the apoptosis of pancreatic cells. Additionally, findings from this study suggest that imbalances in calcium homeostasis could promote pancreatic beta cell death and result in type I diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Molecular and Cellular Endocrinology 05/2015; DOI:10.1016/j.mce.2015.05.017 · 4.24 Impact Factor
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    ABSTRACT: Tight junctions (TJs) form continuous intercellular contacts controlling the paracellular transportation across the cell-to-cell junction. TJ components include the peripheral protein zonula occludens-1 (ZO-1), junctional adhesion molecules (JAMs), and integral proteins such as occludin and claudins. Among the junction proteins, claudins play a major role in regulation of paracellular electrolyte transportation. This study explores the expression and distribution of tight junctions and their regulation during pregnancy. To study the regulation of claudin family, we examined expression of mouse placental tight junction proteins, including claudin-1 to -24, with real-time PCR and Western blotting and distribution of tight junction proteins with immunohistochemistry. Pregnant C57/BL6 mice were used in this study. The pregnant mice were divided into three groups depending on pregnant day (on days 12, 16, and 20 of gestation). Regarding the transcription levels, claudin-1, claudin-2, claudin-4, and claudin-5 expression levels were relatively high compared to other claudin family in all periods of pregnancy. Claudin-4 and 5 expressions, which reduce ion permeability, were increased over a period of time. However, claudin-2 expression, that is the responsive protein for a decrease in paracellular conductance, was decreased. Following this modulation of expression during mid-term pregnancy, we identified endogenous hormonal modulation of claudin family using estrogen receptor antagonist ICI 182,780 and progesterone receptor antagonist RU-486. After administration of ICI and RU-486, expression of claudin-4 mRNA and protein was increased. In addition, immunohistochemistry was performed to identify their localization for inferring permeability in placenta. Due to the function of claudins as effectors of ion transport at the end of regulatory pathways, they must be transducing proteins that modulate the function of claudins and thus link the physiologic inputs to the final effectors. This study will provide the claudin expressions and their localization in the mouse placenta, and their regulation by endogenous hormones. Taken together, the results of this study may contribute to assuming the roles and regulatory mechanism of these tight junction genes regarding maternal-fetal ion transportation in the placenta.
    Steroids 05/2015; 100. DOI:10.1016/j.steroids.2015.05.001 · 2.72 Impact Factor
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    ABSTRACT: Salivary fluid formation is primarily driven by Ca(2+)-activated, apical efflux of chloride into the lumen of the salivary acinus. The anoctamin1 protein is an anion channel with properties resembling the endogenous calcium-activated chloride channels. In order to better understand the role of anoctamin proteins in salivary exocrine secretion, the expression of the ten members of the anoctamin gene family in the mouse submandibular gland was studied. Total RNA extracted from mouse submandibular salivary glands was reverse transcribed using primer pairs to amplify the full-length coding regions of each anoctamin gene and was subcloned into plasmid vectors for DNA sequencing. Alternative splice variants were also screened by polymerase chain reaction using primer pairs that amplified six overlapping regions of the complementary DNA of each anoctamin gene, spanning multiple exons. Multiple anoctamin transcripts were found in the mouse submandibular salivary gland, including full-length transcripts of anoctamin1, anoctamin3, anoctamin4, anoctamin5, anoctamin6, anoctamin9, and anoctamin10. Exon-skipping splicing in the N-terminal exons of the anoctamins1, anoctamin5, and anoctamin6 genes resulted in multiple alternative splice variants. No expression of anoctamin2, anoctamin7, or anoctamin8 was found. The predominant anoctamin transcript expressed in the mouse submandibular gland is anoctamin1ac. The chloride channel protein produced by anoctamin1ac is likely responsible for the Ca(2+)-activated chloride efflux, which is the rate-limiting step in salivary exocrine secretion.
    Journal of periodontal & implant science 04/2015; 45(2):69-75. DOI:10.5051/jpis.2015.45.2.69
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    ABSTRACT: Interferon α (IFN‑α) is a cytokine, produced predominantly in immune cells in response to pathogens, which interferes with viral replication in host cells. Another cytokine hormone, erythropoietin (EPO), is synthesized in interstitial fibroblasts of the kidney and acts as a stimulator for the production of red blood cells. Importantly, the two cytokines have been used in the treatment of certain hematological malignancies, including renal anemia. In the production of recombinant proteins, a transgenic expression system in bovine species is an efficient strategy for pharmaceutical production. In the present study, recombinant constructs capable of producing recombinant human IFN‑α and EPO proteins were established and were generated containing the mammary gland‑specific αS1‑casein promoter region (between ‑175 and +796 nt), as this promoter was revealed to have the highest level of activity in a previous promoter study. In order to minimize developmental toxicity by constitutive exogenous expression, a doxycycline (dox)‑inducible system was introduced to the IFN‑α/EPO‑expressing constructs. Therefore, a unitary tetracycline (tet)‑on the IFN‑α/EPO vector was established, which combined a tet‑on activator cassette controlled by the αS1‑casein promoter, with a responder cassette encoding the IFN‑α/EPO gene, controlled by the tetracycline response element (TRE) promoter. In these systems, the tet‑controlled transactivator is affected by mammary gland‑specific αS1‑casein promoter, and binding of the transcriptional activator to the TRE results in transcription of the downstream IFN‑α/EPO genes in the presence of dox. To assess this, the unitary tet‑on IFN‑α/EPO vector was introduced into a bovine mammary gland cell line (MAC‑T), and the cells were then treated with 0.1‑1 µg/ml dox. A marked increase was observed in the expression levels of IFN‑α/EPO. In addition, bovine transgenic fibroblasts containing a mammary gland‑specific and dox‑inducible IFN‑α/EPO construct were generated. These transgenic fibroblasts may provide a source for somatic cell nuclear transfer for the generation of transgenic cattle producing recombinant human IFN‑α/EPO protein during lactation.
    Molecular Medicine Reports 03/2015; DOI:10.3892/mmr.2015.3483 · 1.48 Impact Factor
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    ABSTRACT: Aromatherapy has been suggested as an alternative therapeutic method for the treatment of atopic dermatitis (AD), eczema and other skin diseases. In the current study, the anti‑atopic properties of the volatile organic compounds of Chamaecyparis obtusa (VOCCo) were examined to determine whether they are amenable for use as a pharmaceutical candidate. The alterations in histological features, serum IgE levels and mast cell infiltration following exposure to VOCCo were determined in a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model. The results of these experiments demonstrated that VOCCo inhibited the development of AD‑like skin lesions by reducing the serum IgE level and mast cell infiltration into the dermal and subcutaneous layers. This was supported by screening of immune cytokine mRNAs, including interleukin (IL)‑1β and IL‑6 from the skin of DNCB‑treated mice. The expression of IL‑1β and IL‑6 in the skin lesions of mice was dose-dependently inhibited by treatment with VOCCo. Furthermore, treatment with VOCCo resulted in the recovery of histopathological features in AD-like skin lesions. These results suggest that VOCCo may have therapeutic and preventive effects for the development of AD.
    Molecular Medicine Reports 03/2015; DOI:10.3892/mmr.2015.3431 · 1.48 Impact Factor
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    ABSTRACT: Embryonic stem (ES) cells have the capacity for self-renewal and differentiation into three germ layers following formation of embryonic bodies (EB). To investigate toxicity of pharmaceutical compounds, five toxic chemicals, indomethacin, dexamethasone, hydroxyurea, 5-fluorouracil, and cytosine arabinoside were applied in mouse ES cells during formation of EBs. Using microscopic evaluation, the size of EBs was reduced in a dose-dependent manner by treatment with pharmaceutical chemicals. While apoptosis-related proteins, cleaved caspase-3 and PARP, were decreased in compound-exposed EBs, necrosis-related protein (Hmgb1) was present in culture media of EBs, indicating that detection of Hmgb1 can result in activation of necrosis by pharmaceutical compounds. While pharmaceutical compounds impaired the differentiation of mES cells linked with spontaneous apoptotic cell death, it was determined that cytotoxic cell damage is necrosis-dependent in mES cells. In addition, an apoptotic transcript (Noxa mRNA) in toxicant-exposed EBs was decreased in parallel with apoptosis-related proteins. Following impairment of apoptosis, differentiation-related markers including un-differentiation (Sox2), endoderm (Hnf4), mesoderm (Bmp4), and ectoderm (Pax6) also fluctuated by treatment with pharmaceutical compounds. Taken together, the data imply that exposure to pharmaceutical compounds results in increased cell death hindering the spontaneous apoptosis of cells to undergo differentiation. Using both characteristics of ES cells like self-renewal or cellular pluripotency and potentials of ES cells for evaluation in toxicity of various compounds, the current study was conducted for establishment of a novel drug screening system beyond hidden virtues of the well-known chemicals. Copyright © 2014 Elsevier B.V. All rights reserved.
    Environmental Toxicology and Pharmacology 12/2014; 39(1):327-338. DOI:10.1016/j.etap.2014.12.003 · 1.86 Impact Factor
  • Hyun Yang, Changhwan Ahn, Eui-Bae Jeung
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    ABSTRACT: Preeclampsia is a pregnancy-specific disease characterized by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. Preeclampsia-like genetic models were also developed by modification of preeclampsia-related genes, such as catechol-O-methyltranferase (COMT). In this study, we induced COMT inhibition in mice during pregnancy in order to reproduce physiological conditions associated with preeclampsia. Expression of the gene known as hypoxia biomarker, HIF-1α, was highly induced in the placenta of this model. The over-expression of HIF-1α demonstrates that our experimental conditions were similar to those of preeclampsia. We measured the expression of several calcium transport genes (CTGs; TRPV5, TRPV6, PMCA1 and CaBP-9k) in the placenta, duodenum and kidney after COMT inhibition on gestation day 17.5 (GD 17.5). In addition, we evaluated the calcium transporters in the kidney, duodenum of non-pregnant female mice. Placental TRPV5, TRPV6 and PMCA1 expressions were down-regulated by COMT inhibitor (ro41-0960). In addition, the reduced PMCA1 expression in the placenta was reversed by calcium supplementation. Duodenal expressions of TRPV5, TRPV6, and PMCA1 were decreased in COMT-inhibited mice, and recovered slightly after calcium supplementation. Renal expression of TRPV5, TRPV6, and PMCA1 was also decreased by COMT inhibition, while it was reversed by calcium supplementation to the level of control. Duodenal- and renal calcium transporting genes, TRPV5, TPRV6, PMCA1 and CaBP-9k, were down-regulated by COMT treatment in female mice. Taken together, these results indicate that physiological changes observed in COMT inhibition were similar to symptoms of preeclampsia, which may be related to disturbance of calcium metabolism during pregnancy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Molecular and Cellular Endocrinology 12/2014; 401(C). DOI:10.1016/j.mce.2014.11.020 · 4.24 Impact Factor
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    ABSTRACT: Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the development of chronic nephrotoxicity. In this study, we investigated CsA treatment induced apoptotic and autophagic cell death in pituitary GH3 cells. CsA treatment (0.1 to 10 µM) decreased survival of GH3 cells in a dose-dependent manner. Cell viability decreased significantly with increasing CsA concentrations largely due to an increase in apoptosis, while cell death rates due to autophagy altered only slightly. Several molecular and morphological features correlated with cell death through these distinct pathways. At concentrations ranging from 1.0 to 10 µM, CsA induced a dose-dependent increase in expression of the autophagy markers LC3-I and LC3-II. Immunofluorescence staining revealed markedly increased levels of both LC3 and lysosomal-associated membrane protein 2 (Lamp2), indicating increases in autophagosomes. At the same CsA doses, apoptotic cell death was apparent as indicated by nuclear and DNA fragmentation and increased p53 expression. In apoptotic or autophagic cells, p-ERK levels were highest at 1.0 µM CsA compared to control or other doses. In contrast, Bax levels in both types of cell death were increased in a dose-dependent manner, while Bcl-2 levels showed dose-dependent augmentation in autophagy and were decreased in apoptosis. Manganese superoxide dismutase (Mn-SOD) showed a similar dose-dependent reduction in cells undergoing apoptosis, while levels of the intracellular calcium ion exchange maker calbindin-D9k were decreased in apoptosis (1.0 to 5 µM CsA), but unchanged in autophagy. In conclusion, these results suggest that CsA induction of apoptotic or autophagic cell death in rat pituitary GH3 cells depends on the relative expression of factors and correlates with Bcl-2 and Mn-SOD levels.
    PLoS ONE 10/2014; 9(10):e108981. DOI:10.1371/journal.pone.0108981 · 3.53 Impact Factor
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    ABSTRACT: To determine whether exogenous amino acids affect gene transcription patterns in parthenogenetic porcine embryos, we investigated the effects of amino acid mixtures in culture medium. Parthenogenetic embryos were cultured in PZM3 medium under four experimental conditions: 1) control (no amino acids except L-glutamine and taurine); 2) nonessential amino acids (NEAA); 3) essential amino acids (EAA); and 4) NEAA and EAA. The rate of development of embryos to the four-cell stage was not affected by treatment. However, fewer (P<0.05) embryos cultured with EAA (12.8%) reached the blastocyst stage as compared with the control group (25.6%) and NEAA group (30.3%). Based on these findings, we identified genes with altered expression in parthenogenetic embryos exposed to medium with or without EAAs. The results indicated that EAA influenced gene expression patterns, particularly those of imprinted genes (e.g., H19, IGF2R, PEG1, XIST). However, NEAAs did not affect impaired imprinted gene expressions induced by EAA. The results also showed that mechanistic target of rapamycin (MTOR) mRNA expression was significantly increased by EAA alone as compared with control cultures, and that the combined treatment with NEAA and EAA did not differ significantly from those of control cultures. Our results revealed that gene transcription levels in porcine embryos changed differentially depending on the presence of EAA or NEAA. However, the changes in the H19 mRNA observed in the parthenogenetic blastocysts expression level was not related to the DNA methylation status in the IGF2/H19 domain. The addition of exogenous amino acid mixtures affected not only early embryonic development, but also gene transcription levels, particularly those of imprinted genes. However, this study did not reveal how amino acids affect expression of imprinted genes under the culture conditions used. Further studies are thus required to fully evaluate how amino acids affect transcriptional regulation in porcine embryos.
    PLoS ONE 09/2014; 9(9):e106549. DOI:10.1371/journal.pone.0106549 · 3.53 Impact Factor
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    ABSTRACT: Inducible cyclic AMP (cAMP) early repressor (ICER) Iγ acts as an endogenous inhibitor and disrupts the transcriptional regulation of cAMP response element binding protein (CREBP) responsive genes. Since the overexpression of ICER Iγ induces severe diabetes in a transgenic mouse model, with characteristics similar to human diabetes mellitus, an ICER Iγ construct containing an adjustable pancreas tissue specific promoter was utilized in the present study. Using the human insulin promoter region, a doxycycline (dox)‑inducible ICER Iγ expression system was established using the tetracycline (tet)-controlled transactivator (tTA) with a TA response element (TRE) promoter. A unitary tet-on system that combined a tet-on activator cassette was also developed and was controlled by the human insulin promoter with a responder cassette containing genes encoding ICER Iγ regulated by the TRE promoter. To determine whether dox-enhanced ICER Iγ expression affected insulin production, the unitary tet-on ICER Iγ vector was introduced into a mouse pancreatic β-cell line and then the cells were treated with 0.1-1 mg/ml dox. The results revealed a robust increase in ICER Iγ expression and decreased insulin production. Therefore, this in vitro system may be useful for studying human diabetes mellitus and pre-diabetes using tissue-specific promoters and a dox-inducible transgene. In addition, porcine transgenic fibroblasts containing dox-inducible ICER Iγ were generated. These fibroblasts may serve as a cell source for somatic cell nuclear transfer to generate a porcine model of human diabetes mellitus.
    Molecular Medicine Reports 05/2014; 10(2). DOI:10.3892/mmr.2014.2255 · 1.48 Impact Factor
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    ABSTRACT: Calciotropic hormones were thought to facilitate calcium transfer through active transcellular or passive paracellular pathway for calcium homeostasis. While calcium transport proteins such as CaBP-28 k, TRPV5, NCX1, PMCA1b are involved in calcium reabsorption of the renal tubule using transcellular transport, tight junction proteins are known as critically related to calcium absorption through paracellular pathway. The regulation of each pathway for calcium transport was well studied but the correlation was not. It is expected that present study will provide new information about the link between transcellular and paracellular pathway within renal tubules. Transcripts and proteins of tight junction related genes (occludin, ZO-1, and claudins) were examined in CaBP-9 k-and/or-28 k-deficient mice as well as the effect of dietary calcium and/or vitamin D supplementation. With a normal diet, the transcriptional and translational expressions of most tight junction proteins in the kidney was not significantly changed but with a calcium- and vitamin D-deficient diet, and they were significantly increased in the kidney of the CaBP-28 k and CaBP-9 k/28 k double KO (DKO) mice. In these genotypes, the increase of tight junction related transcripts and proteins are referred to as an evidence explaining correlation between transcellular transport and paracellular pathway. These findings are particularly interesting in evidences that insufficient transcellular calcium transports are compensated by paracellular pathway in calcium or calcium/vitamin D deficient condition, and that both transcellular and paracellular pathways functionally cooperate for calcium reabsorption in the kidney.
    BMC Biochemistry 03/2014; 15(1):6. DOI:10.1186/1471-2091-15-6 · 1.94 Impact Factor
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    ABSTRACT: Claudins (CLDNs) are tetraspan transmembrane proteins, which are components of tight junctions. The CLDN family is composed of 27 members that are responsible for paracellular transport and certain CLDNs form charge‑selective ion channels. CLDNs have two extracellular loops, and the charge of the first extracellular loop determines the ion selectivity of each CLDN. Although the expression and function of each CLDN have been previously investigated, the distribution of CLDNs in various target organs remains to be determined. In the present study, the tissue‑specific mRNA distribution of CLDNs (1‑5, 7‑8, 10a and b, 11‑12, 14‑17 and 19) in the duodenum, ileum, colon, kidney, liver and lung were defined. Among the tested CLDNs, CLDN1, 2, 12 and 16 were selected for further investiagtion. It was observed that CLDN1, CLDN2 and CLDN12 transcripts and proteins were particularly abundant in the investigated organs. Notably, immune‑reactive CLDN16 was detected in a tissue‑specific manner and shown in the renal tubules and portal vein. The tested CLDNs were localized to intercellular apical junctions in the epithelium of the intestine, renal tubule and bronchus. Based on this novel information, the presence of several types of CLDNs is of interest as CLDNs may promote or dampen the paracellular diffusion of specific ions.
    Molecular Medicine Reports 03/2014; 9(5). DOI:10.3892/mmr.2014.2031 · 1.48 Impact Factor
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    ABSTRACT: The transient receptor potential channels are membrane-binding proteins that are nonselectively permeable for cations, such as Ca(2+) and Mg(2+), in numerous mammalian cells. The extracellular or intracellular ions play key roles in physiological functions including muscle contraction, cytokine production, insulin release, and apoptosis. Although transient receptor potential melastatin (TRPM) channels are implicated in nonreproductive tissues, the presence of TRPM2 has been reported in endometrium of uterus. To examine whether the expression of TRPM2 gene in uterus is due to gonadal steroid hormones or hormone-independent effect, the uterine TRPM2 gene was monitored in uterus of mature rat during estrous cycle and of immature rat after treatment with gonadal steroid estrogen (E2), progesterone (P4) with/without estrogen receptor antagonist Imperial Chemical Industries (ICI) 182780. We examined real-time polymerase chain reaction, Western blot, and immunohistochemistry to demonstrate the expression and localization of the uterine TRPM2 gene. The level of TRPM2 messenger RNA and protein are dramatically induced at proestrus, then dropped to base line levels at metestrus, and restored its level at diestrus. The results imply that uterine TRPM2 expression levels are regulated by gonadal steroid hormone E2. Moreover, the E2-induced TRPM2 expression is inhibited by cotreatment with ICI 182780 or P4. Furthermore, the immune-reactive TRPM2 is observed in myometrium and stromal cell of endometrium and also showed alterations in TRPM2 expression during estrus cycle. This study suggests that TRPM2 may be involved in calcium absorption or uterine contraction and the latter may be related to implantation or labor by endogenous sex steroid hormones.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2014; 21(10). DOI:10.1177/1933719114525276 · 2.18 Impact Factor
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    ABSTRACT: Canines are considered the most authentic model for studying multifactorial human diseases, as these animals typically share a common environment with man. Somatic cell nuclear transfer (SCNT) technology along with genetic engineering of nuclear donor cells provides a unique opportunity for examining human diseases using transgenic canines. In the present study, we generated transgenic canines that overexpressed the human amyloid precursor protein (APP) gene containing well-characterized familial Alzheimer's disease (AD) mutations. We successfully obtained five out of six live puppies by SCNT. This was confirmed by observing the expression of green fluorescence protein in the body as a visual transgenic marker and the overexpression of the mutated APP gene in the brain. The transgenic canines developed AD-like symptoms, such as enlarged ventricles, an atrophied hippocampus, and β-amyloid plaques in the brain. Thus, the transgenic canines we created can serve as a novel animal model for studying human AD.
    International Journal of Molecular Medicine 01/2014; 33(4). DOI:10.3892/ijmm.2014.1636 · 1.88 Impact Factor
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    ABSTRACT: Korean red ginseng extract (RGE) is one of the most popular natural herbs modulating the immune system. Although the effects of RGE on immunity have been reported, its effects on inflammasomes, multi-protein complexes that activate caspase-1 to induce maturation of interleukin (IL)-1β, have not been studied yet. In this study, we elucidated the effect of RGE on inflammasome activation using mouse and human macrophages. In our results, RGE inhibited IL-1β maturation resulting from NLRP3 inflammasome activation in both in vitro and in vivo models. In addition, RGE strongly attenuated IL-1β secretion as well as pathogen clearance via pyroptotic cell death by macrophages through inhibition of AIM2 inflammasome activation. Ginsenosides Rg1 and Rh3 were suggested as inhibitors of the inflammasome activation. Thus, we demonstrated that RGE inhibits both NLRP3 and AIM2 inflammasome activation, with predominant involvement of the AIM2 inflammasome.
    Immunology letters 01/2014; 158(1-2). DOI:10.1016/j.imlet.2013.12.017 · 2.37 Impact Factor
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    Eui-Ju Hong, Eui-Bae Jeung
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    ABSTRACT: Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.
    12/2013; 29(4):221-227. DOI:10.5487/TR.2013.29.4.221
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    ABSTRACT: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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    ABSTRACT: Lentinus (L.) edodes (shiitake mushroom) is used as a traditional medicine in Asia. One of the components of L. edodes, eritadenine (an adenosine analog alkaloid), has been shown to reduce cholesterol levels. The hypocholesterolemic action of eritadenine appears to be achieved through the modification of hepatic phospholipid metabolism. In the present study, the effects of L. edodes in a mouse model of hypercholesterolemia were investigated. Hypercholesterolemia was induced by the consumption of a high-fat diet (HFD). The animals were divided into six groups, which were fed a normal diet, HFD alone, HFD containing eritadenine [10 mg/kg of body weight (BW)] or HFD with 5, 10 or 20% L. edodes, respectively, for 4 weeks (from 5 to 9 weeks of age). The mice in the six groups had similar BW gains. Total serum cholesterol (T-CHO), low-density lipoprotein (LDL) and triglyceride (TG) levels were increased in the HFD-fed group compared with those in the normal diet group. However, the levels of high-density lipoprotein (HDL) were not significantly altered. In mice treated with L. edodes (5, 10 or 20%), the T-CHO, LDL and TG serum levels were reduced in a dose-dependent manner. The mRNA expression of cholesterol 7-α-hydroxylase 1 (CYP7A1) was decreased in hypercholesterolemic mice and increased by eritadenine and L. edodes (5, 10 and 20%) supplementation. In liver tissues, it was observed that lipid accumulation was reduced by treatment with eritadenine and L. edodes. In addition, it was revealed that the formation of atherosclerotic plaques due to the HFD was also suppressed by eritadenine and L. edodes. The results of the study indicated that the consumption of an HFD may inhibit CYP7A1 expression in the liver by increasing serum T-CHO, LDL and TG levels. L. edodes may help regulate lipid metabolism, suggesting that this fungus ameliorates hypercholesterolemia in mice by regulating CYP7A1 expression in the liver.
    Experimental and therapeutic medicine 12/2013; 6(6):1409-1413. DOI:10.3892/etm.2013.1333 · 0.94 Impact Factor
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    Eui-Ju Hong, Eui-Bae Jeung
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    ABSTRACT: Calbindin-D9k (CaBP-9k) binds calcium with high affinity and regulates the distribution of free calcium in the cytoplasm. The expression of CaBP-9k is detected primarily in intestine that is vitamin D target tissue, and accumulates in the enterocytes of the duodenal villi. These enterocytes are the clearest example of vitamin D responsive cells, and the presence of CaBP-9k within them accentuates calcium absorption mediated by active transcellular calcium transport. It has been well established that the expression of CaBP-9k is mediated with vitamin D response element on its promoter and it regulates the amount of intracellular calcium in order to prevent cell death from reaching the toxicity of free calcium. There is now little doubt that glucocorticoid also decreases CaBP-9k expression in duodenal epithelial cells. In addition, it was reported that the level of CaBP-9k gene in enterocytes is increased in pregnancy when the plasma estradiol concentration is generally associated with a concomitant increase. Although calcium homeostasis was not disturbed in mice lacking the CaBP-9k gene, we found that CaBP-9k has a buffering role of free calcium in the cytosolic environment beyond that of calcium transfer. To expand our knowledge of the biological functions of CaBP-9k, our research has focused on defining the biological significance of intracellular CaBP-9k. Our findings suggest that the CaBP-9k gene is involved in compensatory induction of other calcium transporter genes in duodenal epithelial cells. This article summarizes the findings from recent studies on the expression and the functions of CaBP-9k in the small intestine.
    International Journal of Molecular Sciences 12/2013; 14(12):23330-40. DOI:10.3390/ijms141223330 · 2.34 Impact Factor

Publication Stats

3k Citations
489.99 Total Impact Points

Institutions

  • 2002–2015
    • Chungbuk National University
      • College of Veterinary Medicine
      Chinsen, Chungcheongbuk-do, South Korea
  • 2012
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
  • 2003–2011
    • University of British Columbia - Vancouver
      • • Department of Medicine
      • • Department of Obstetrics and Gynaecology
      Vancouver, British Columbia, Canada
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • Laboratory of Development and Differentiation
      Ansan, Gyeonggi, South Korea
  • 2005
    • Seoul National University
      • College of Agriculture and Life Sciences
      Seoul, Seoul, South Korea