• Title/Summary/Keyword: Binding Potential

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ErbB2 kinase domain is required for ErbB2 association with β-catenin (ErbB2의 kinase 영역이 β-catenin과 ErbB2의 결합에 필요하다)

  • Ha, Nam-Chul;Xu, Wanping;Neckers, Len;Jung, Yun-Jin
    • Journal of Life Science
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    • v.17 no.3 s.83
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    • pp.356-361
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    • 2007
  • To investigate the region of ErbB2 for the $ErbB2-{\beta}-catenin$ interaction, a proteasome $resistant-{\beta}-catenin$ and various ErbB2 constructs were transfected in COS7 cells. ErbB2 proteins were immunoprecipitated, and coimmunoprecipitated ${\beta}-catenin$ was examined by Western blotting. ${\beta}-catenin$ coimmunoprecipitated with full length ErbB2. Of the truncated ErbB2 proteins DT (1-1123), DHC (1-1031) and DK (1-750), the ErbB2 constructs containing the kinase domain, DT and DHC, precipitated together with ${\beta}-catenin$ but DK containing no kinase domain did not. To further test the requirement of the kinase domain for ${\beta}-catenin-ErbB2$ interaction, the presence of ${\beta}-catenin$ in the immunocomplex was examined following transfection with an ErbB2 mutant (${\triangle}750-971$) whose kinase domain is internally deleted and subsequent immunoprecipitation of the ErbB2 mutant. ${\beta}-catenin$ was not detected in the immunocomplex. These results suggest that the ErbB2 kinase domain comprises a potential site for ${\beta}-catenin$ binding to the receptor tyrosine kinase.

Whole genome MBD-seq and RRBS analyses reveal that hypermethylation of gastrointestinal hormone receptors is associated with gastric carcinogenesis

  • Kim, Hee-Jin;Kang, Tae-Wook;Haam, Keeok;Kim, Mirang;Kim, Seon-Kyu;Kim, Seon-Young;Lee, Sang-Il;Song, Kyu-Sang;Jeong, Hyun-Yong;Kim, Yong Sung
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.1.1-1.14
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    • 2018
  • DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

Loganin Inhibits α-MSH and IBMX-induced Melanogenesis by Suppressing the Expression of Tyrosinase in B16F10 Melanoma Cells (마우스 흑색종 B16F10세포에서 loganin의 티로시나아제 발현 억제를 통한 멜라닌 생성 억제에 대한 기전연구)

  • Jung, Hee Jin;Bang, EunJin;Kim, Byeong Moo;Jeong, Seong Ho;Lee, Gil Han;Chung, Hae Young
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1200-1207
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    • 2019
  • Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and $20{\mu}m$. Cell viability assays confirmed that doses of loganin up to $20{\mu}m$ were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with ${\alpha}-MSH$ and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by ${\alpha}-MSH$ and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.

Bioaccumulation of Heavy Metals in Intestine of Nacella concinna (남극삿갓조개 (Nacella concinna) 장의 중금속 축적에 관한 연구)

  • Lee, Yong-Seok;Jo, Yong-Hun;Han, Yeon-Soo;Kho, Weon-Gyu;Ahn, In-Young;Jeong, Kye-Heon
    • The Korean Journal of Malacology
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    • v.22 no.1 s.35
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    • pp.87-95
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    • 2006
  • Immunohistochemical and ultrastuructural experiments were conducted to find out heavy metal accumulation in the intestine of an Antarctic gastropod Nacella concinna. According to the immune-histochemical experiment the apical cytoplasm of the intestinal epithelium showed positive reactions to anti-MT (rnotallothionein), indicating the presence of MT, a metal-binding protein involved in metal detoxifying process. In the transmission electron microscopic observations, the epithelial cells of the intestine exposed to Cd for over three hours showed irregular nuclear membranes, secretory granules, and probable metal granules. According to the SEM-EDS experiments on the intestine, concentration of Pb in the apical epithelium was in inverse proportion to that in the intestinal lumen. After exposing to Cd for over three days, S was rapidly reduced. Ca and Zn were rapidly increased after exposure to Cd. These elements are supposed to be concerned with the MT-reaction in the intestine. laken together, these data suggest that N. concinna could be used as a potential biomarker species.

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Photoelectron Spectroscopy Study of the Semiconductor Electrode Nanomaterials for the Dye Synthesized Solar Cell (염료감응 태양전지 전극용 반도체 나노 물질의 광전자분광 연구)

  • Kim, Hyun Woo;Lee, Eunsook;Kim, D.H.;Seong, Seungho;Kang, J.-S.;Moon, S.Y.;Shin, Yuju
    • Journal of the Korean Magnetics Society
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    • v.25 no.5
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    • pp.156-161
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    • 2015
  • The electronic structures of the potential candidate semiconductor nanoparticles for dye-sensitized solar cell (DSSC), such as $ZnSnO_3$ and $Zn_2SnO_4$, have been investigated by employing X-ray photoemission spectroscopy (XPS). The measured X-ray diffraction patterns show that $ZnSnO_3$ and $Zn_2SnO_4$ samples have the single-phase ilmenite-type structure and the inverse spinel structure, respectively. The measured Zn 2p and Sn 3d core-level XPS spectra reveal that the valence states of Zn and Sn ions are divalent (Zn 2+) and tetravalent (Sn 4+), respectively, in both $ZnSnO_3$ and $Zn_2SnO_4$. On the other hand, the shallow core-level measurements show that the binding energies of Sn 4d and Zn 3d core levels in $ZnSnO_3$ are lower than those in $Zn_2SnO_4$. This work provides the information on the valence states of Zn and Sn ions and their chemical bonding in $ZnSnO_3$ and $Zn_2SnO_4$.

Inhibitory Effects of Illicium verum Hooker fil. Dichloromethane Fractions on Adipocyte Differentiation (팔각회향 dichloromethane 분획물에 의한 지방세포 분화 억제 효과)

  • Jeong, Hyun Young;Jeong, In Kyo;Kim, Nam Ju;Yun, Hee Jung;Park, Jung Ha;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.29 no.4
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    • pp.447-454
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    • 2019
  • Fat accumulation in adipocytes occurs through the process of adipogenesis in which preadipocytes differentiate into adipocytes. Obesity is a metabolic disorder caused by excessive accumulation of fat in the body, which increases the incidence of cardiovascular diseases, hypertension, type 2 diabetes, hyperlipidemia, and various cancers. Recently, inhibition of adipocyte differentiation was shown to be a potential antiobesity strategy. In this study, the inhibitory effect of dichloromethane fractions from Illicium verum Hooker fil. water extract on the differentiation of 3T3-L1 preadipocytes to adipocytes was investigated. Dichloromethane fractions from I. verum Hooker fil. significantly inhibited adipocyte differentiation when applied during the adipocyte differentiation process, as assessed by measuring fat accumulation using Oil-red O staining. In addition, dichloromethane fractions from I. verum Hooker fil. reduced important adipogenic transcription factors, such as CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and peroxisome proliferator activated receptor ${\gamma}$ ($PPAR{\gamma}$). The expression of FAS and LPL, which are terminal differentiation markers of mature adipocytes, was also reduced in the 3T3-L1 adipocytes treated with dichloromethane fractions from I. verum Hooker fil. In addition, the treatment significantly inhibited mitotic clonal expansion, which is essential for adipocyte differentiation, by arresting the G1 phase of the cell cycle. Taken together, these results suggest that dichloromethane fractions from I. verum Hooker fil. may be a natural material with antiobesity effects.

Protective effects of Korean Red Ginseng against sub-acute immobilization stress-induced testicular damage in experimental rats

  • Lee, Sang-Ho;Choi, Kyung-Hwa;Cha, Kyu-Min;Hwang, Seock-Yeon;Park, Un-Kyu;Jeong, Min-Sik;Hong, Jae-Yup;Han, Chang-Kyun;In, Gyo;Kopalli, Spandana Rajendra;Kim, Si-Kwan
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.125-134
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    • 2019
  • Background: Excessive stress causes varied physiological and psychological disorders including male reproductive problems. Here, we attempted to investigate the protective effects of Korean Red Ginseng (Panax ginseng Meyer; KRG) against sub-acute immobilization stress-induced testicular damage in experimental rats. Methods: Male rats (age, 4 wk; weight, 60-70 g) were divided into four groups (n = 8 in each group): normal control group, immobilization control group, immobilization group treated with 100 mg/kg of KRG daily, and immobilization group treated with 200 mg/kg of KRG daily. Normal control and immobilization control groups received vehicle only. KRG (100 mg/kg and 200 mg/kg) was mixed in the standard diet powder and fed daily for 6 mo. Parameters such as organ weight, blood chemistry, sperm kinematic values, and expression levels of testicular-related molecules were measured using commercially available kits, Western blotting, and reverse transcription polymerase chain reaction. Results: Data revealed that KRG restored the altered testis and epididymis weight in immobilization stress-induced rats significantly (p < 0.05). Further, KRG ameliorated the altered blood chemistry and sperm kinematic values when compared with the immobilization control group and attenuated the altered expression levels of spermatogenesis-related proteins (nectin-2, cAMP responsive element binding protein 1, and inhibin-${\alpha}$), sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor), and antioxidant-related enzymes (glutathione S-transferase m5, peroxiredoxin-4, and glutathione peroxidase 4) significantly in the testes of immobilization stress-induced rats. Conclusion: KRG protected immobilization stress-induced testicular damage and fertility factors in rats, thereby indicating its potential in the treatment of stress-related male sterility.

Hepatic microRNAome reveals potential microRNA-mRNA pairs association with lipid metabolism in pigs

  • Liu, Jingge;Ning, Caibo;Li, Bojiang;Li, Rongyang;Wu, Wangjun;Liu, Honglin
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.9
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    • pp.1458-1468
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    • 2019
  • Objective: As one of the most important metabolic organs, the liver plays vital roles in modulating the lipid metabolism. This study was to compare miRNA expression profiles of the Large White liver between two different developmental periods and to identify candidate miRNAs for lipid metabolism. Methods: Eight liver samples were collected from White Large of 70-day fetus (P70) and of 70-day piglets (D70) (with 4 biological repeats at each development period) to construct sRNA libraries. Then the eight prepared sRNA libraries were sequenced using Illumina next-generation sequencing technology on HiSeq 2500 platform. Results: As a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55 down- and 61 up-regulated miRNAs were shown to be significantly differentially expressed (DE). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that these DE miRNAs were mainly involved in growth, development and diverse metabolic processes. They were predicted to regulate lipid metabolism through adipocytokine signaling pathway, mitogen-activated protein kinase, AMP-activated protein kinase, cyclic adenosine monophosphate, phosphatidylinositol 3 kinase/protein kinase B, and Notch signaling pathway. The four most abundantly expressed miRNAs were miR-122, miR-26a and miR-30a-5p (miR-122 only in P70), which play important roles in lipid metabolism. Integration analysis (details of mRNAs sequencing data were shown in another unpublished paper) revealed that many target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p, and miR-98) might be critical regulators in lipid metabolic process, including acyl-CoA synthetase long chain family member 4, ATP-binding casette A4, and stearyl-CoA desaturase. Thus, these miRNAs were the promising candidates for lipid metabolism. Conclusion: Our study provides the main differences in the Large White at miRNA level between two different developmental stages. It supplies a valuable database for the further function and mechanism elucidation of miRNAs in porcine liver development and lipid metabolism.

Analysis of Capacitance and Mobility of ZTO with Amorphous Structure (비정질구조의 ZTO 박막에서 커패시턴스와 이동도 분석)

  • Oh, Teresa
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.6
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    • pp.14-18
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    • 2019
  • The conductivity of a semiconductor is primarily determined by the carriers. To achieve higher conductivity, the number of carriers should be high, and an energy trap level is created so that the carriers can cross the forbidden zone with low energy. Carriers have a crystalline binding structure, and interfacial mismatching tends to make them less conductive. In general, high-concentration doping is typically used to increase mobility. However, higher conductivity is also observed in non-orthogonal conjugation structures. In this study, the phenomena of higher conductivity and higher mobility were observed with space charge limiting current due to tunneling phenomena, which are different from trapping phenomena. In an atypical structure, the number of carriers is low, the resistance is high, and the on/off characteristics of capacitances are improved, thus increasing the mobility. ZTO thin film improved the on/off characteristics of capacitances after heat treating at $150^{\circ}C$. In charging and discharging tests, there was a time difference in the charge and discharging shapes, there was no distinction between n and p type, and the bonding structure was amorphous, such as in the depletion layer. The amorphous bonding structure can be seen as a potential barrier, which is also a source of space charge limiting current and causes conduction as a result of tunneling. Thus, increased mobility was observed in the non-structured configuration, and the conductivity increased despite the reduction of carriers.

Study on the fatty acid profile of phospholipid and neutral lipid in Hanwoo beef and their relationship to genetic variation

  • Beak, Seok-Hyeon;Lee, Yoonseok;Lee, Eun Bi;Kim, Kyoung Hoon;Kim, Jong Geun;Bok, Jin Duck;Kang, Sang-Kee
    • Journal of Animal Science and Technology
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    • v.61 no.2
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    • pp.69-76
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    • 2019
  • Maize which has very high omega-6 fatty acid content has been used as a main feed grain for Hanwoo beef production to increase marbling, and thus omega-6 to omega-3 fatty acids ratio in Hanwoo beef is expected to be biased. To elucidate the current status of omega fatty acids ratio in Hanwoo beef, fatty acid profiles of neutral lipid and phospholipid fraction were analyzed separately using 55 Hanwoo steers' longissimus dorsi muscle slaughtered at Pyeongchang, Korea from Oct. to Nov. 2015. In addition, an association study was conducted to evaluate associations between single nucleotide polymorphism (SNP) markers from references and omega fatty acid profiles in phospholipid of Hanwoo beef samples using analysis of variance (ANOVA). In neutral lipid fraction, composition of saturated and monounsaturated fatty acids was higher and polyunsaturated fatty acids was lower compared to those in phospholipid fraction. The mean n-6/n-3 ratios of Hanwoo were $56.059{\pm}16.180$ and $26.811{\pm}6.668$ in phospholipid and neutral lipid, respectively. There were three SNPs showing statistically significant associations with omega fatty acid content. GA type of rs41919985 in fatty acid synthase (FASN) was significantly associated with the highest amount of C20:5 n-3 (p = 0.031). CC type of rs41729173 in fatty acid-binding protein 4 (FABP4) was significantly associated with the lowest amount of C22:2n-6 (p = 0.047). AG type of rs42187261 in FADS1 was significantly linked to the lowest concentration of C20:4 n-6 (p = 0.044). The total n-6/n-3 ratio of the steer which has all four SNP types in above loci (27.905) was much lower than the mean value of the total n-6/n-3 ratio in phospholipid of the 55 Hanwoo steers ($56.059{\pm}16.180$). It was found that phospholipid and neutral lipid of Hanwoo have very high n-6/n-3 ratios compared to the reported data from different cow breeds. Four SNPs in genes related with fatty acid metabolism showed significant associations with the fatty acid profile of phospholipid and may have potential as SNP markers to select Hanwoo steers in terms of n-6/n-3 balance in the future.