• Title/Summary/Keyword: HNF4

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Association of Hepatocyte Nuclear Factor-$4{\alpha}$ (HNF-$4{\alpha}$) Polymorphisms (rs1884614) with Type 2 Diabetes in Korean Population

  • Kim, Su-Won;Yoo, Min
    • Biomedical Science Letters
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    • v.15 no.1
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    • pp.101-103
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    • 2009
  • The hepatocyte nuclear factor-$4{\alpha}$ (HNF-$4{\alpha}$), transcription factor involved in the regulation of serum lipid and glucose levels, has recently been reported to be associated with type 2 diabetes. Therefore, we investigated the genotype for the rs1884614 of HNF-$4{\alpha}$ gene in Korean population and compared genotype of patients with control group. 100 patients (Male 63, Female 37), who previously underwent type 2 diabetes (T2DM) and 100 controls (Male 36, Female 64) participated in this study. According to our present study there was no association between rs1884614 polymorphism in HNF-$4{\alpha}$ gene and T2DM in Koreans although other reports showed that HNF-$4{\alpha}$ polymorphisms might be associated with the pathogenesis of T2DM in Pima Indians et al. We assume that this finding should contribute to understanding of type 2 diabetes in Korean population in detail at genetic level.

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Association of Hepatocyte Nuclear factor-4α Polymorphisms with Type 2 Diabetes in Koreans (한국인에서의 hepatocyte nuclear factor-4α의 유전자 다형성과 제2형 당뇨병과의 연관성)

  • Kim, Su-Won;Yoo, Min
    • Journal of Life Science
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    • v.19 no.3
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    • pp.362-365
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    • 2009
  • Type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. The hepatocyte nuclear factor-$4{\alpha}$ (HNF-$4{\alpha}$), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. Therefore, we investigated the genotype for the C>T polymorphism at position 12352 of the HNF-$4{\alpha}$ gene in Koreans and compared patient genotypes with those of the control group. 100 patients (63 males, 37 females) with a history of type 2 diabetes (T2DM) and 100 controls (36 males, 64 females) participated in this study. There was no association between 12352 C>T polymorphism in the HNF-$4{\alpha}$ gene and T2DM. The present study shows that HNF-$4{\alpha}$ 12352 C>T polymorphism may not be associated with the pathogenesis of T2DM. Further studies with larger populations may be needed for the development of diagnostic methods at a genetic level such as DNA chip.

Identification and Functional Characterization of P159L Mutation in HNF1B in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5)

  • Kim, Eun Ky;Lee, Ji Seon;Cheong, Hae Il;Chung, Sung Soo;Kwak, Soo Heon;Park, Kyong Soo
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.240-246
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    • 2014
  • Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

Lactobacillus acidophilus NS1 Reduces Phosphoenolpyruvate Carboxylase Expression by Regulating HNF4α Transcriptional Activity

  • Park, Sung-Soo;Yang, Garam;Kim, Eungseok
    • Food Science of Animal Resources
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    • v.37 no.4
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    • pp.529-534
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    • 2017
  • Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited $HNF4{\alpha}-induced$ PEPCK promoter activity in HepG2 cells without change of $HNF4{\alpha}$ mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating $HNF4{\alpha}$ transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.

Association of SNPs in the HNF4α Gene with Growth Performance of Korean Native Chickens (한국 재래계의 HNF4α 유전자 내 SNP와 성장과의 연관성 분석)

  • Yang, Song-Yi;Choi, So-Young;Hong, Min-Wook;Kim, Hun;Kwak, Kyeongrok;Lee, Hyojeong;Jeong, Dong Kee;Sohn, Sea Hwan;Hong, Yeong Ho;Lee, Sung-Jin
    • Korean Journal of Poultry Science
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    • v.45 no.4
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    • pp.253-260
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    • 2018
  • The hepatocyte nuclear factor 4 alpha ($HNF4{\alpha}$) gene is related to lipid transport, including abdominal fat and growth, in chickens. Interestingly, the A543G SNP within the $HNF4{\alpha}$ gene has previously been reported to be associated with body weight in both broilers and Korean native chickens (KNCs). However, its exact position within the HNF4 is not yet reported. This study aimed to identify the position of the A543G SNP and to identify additional SNPs that can be used as genetic markers in KNCs. A total of 128 KNCs were used for the sequencing and analysis of these genetic associations. As a result, A543G SNP was located in intron 4 of the $HNF4{\alpha}$ gene; it is reported as rs731246957 in the NCBI database. Fourteen SNPs were detected in the sequenced portion of the $HNF4{\alpha}$ gene; three of these, rs731246957, rs736159604 and new SNP, intron 6 (249), were significantly related with growth in the chickens. In this study, the TT genotype of rs731246957, previously reported as A543G SNP, the GG genotype of rs736159604 and GT of new SNP have are highly associated with body weight from birth to 40 weeks of age in KNCs (P<0.01). These results suggest that rs736159604, rs731246957 and intron 6 (249) SNPs within the $HNF4{\alpha}$ gene could function as growth-related markers in the selective breeding of KNCs.

Expression of Exogenous Human Hepatic Nuclear Factor-$1{\alpha}$ by a Lentiviral Vector and Its Interactions with Plasmodium falciparum Subtilisin-Like Protease 2

  • Liao, Shunyao;Liu, Yunqiang;Zheng, Bing;Cho, Pyo-Yun;Song, Hyun-Ok;Lee, Yun-Seok;Jung, Suk-Yul;Park, Hyun
    • Parasites, Hosts and Diseases
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    • v.49 no.4
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    • pp.431-436
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    • 2011
  • The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-$1{\alpha}$ is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-$1{\alpha}$ in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-$1{\alpha}$ expressed by a lentiviral vector (LV HNF-$1{\alpha}$) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-$1{\alpha}$ was observed to influence promoter activity, suggesting that host HNF-$1{\alpha}$ interacts with the Sub2 gene.

Characteristics of Microbial Abundances in Hypoxic Water of Brackish take Shihwa

  • Choi, Dong.H.;Na, Sang.C.;Park, Yong.C.;Huh, Sung.H.;Cho, Byung.C.
    • Journal of the korean society of oceanography
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    • v.34 no.4
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    • pp.236-240
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    • 1999
  • A preliminary study was carried out to find characteristics of microbial trophic relations in hypoxic waters of Lake Shihwa in May and August 1996. Abundances of bacteria, viruses, and heterotrophic nanoflagellates (HNF) and HNF grazing on bacteria were measured. Dissolved O$_2$ (DO) saturation ranged from 13 to 34% in the bottom waters, and % of DO saturation strongly correlated with salinity. Ratios of HNF-to-bacteria abundance (42-118${\times}$10$^{-5}$) and biomass (0.06-0.25), and ratios of virus-to-bacteria abundance (110-297) in the hypoxic water were similar to those found in the surface layer, indicating similar structures of microbial abundances and trophic functions in hypoxicand surface waters during the study period. In the hypoxic water, an energy flow from organic matter to bacteria to HNF might operate as equally as in oxic surface layer.

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The Study on the Seasonal Variation of Microbial Community in Kyeonggi Bay, Korea 1. Bacteria and Heterotrophic nanoflagellates (경기만 수역에서 미세생물 군집의 계절적 변동 연구 I. 박테리아와 종속영양 미소 편모류)

  • 양은진;최중기;현정호
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.8 no.1
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    • pp.44-57
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    • 2003
  • Seasonal variations of bacterial abundance and production, heterotrophic nanoflagellate (HNF) abundance and HNF ingestion rates on bacteria using FLB together with environmental variables were investigated at intervals of a month in Kyeonggi Bay from December 1991 to November 1998. Bacterial abundance and production ranged from 0.38$\times$10$^{9}$ ~ 3.25$\times$10$^{9}$ cells 1$^{-1}$ (average 1.19$\pm$0.69$\times$10$^{9}$ cells 1$^{-1}$ ) and from 1.51 to 20.4 cells 1$^{-1}$ h$^{-1}$ (average 6.04$\pm$ 1.88$\times$10$^{6}$ cells 1$^{-1}$ h$^{-1}$ ), respectively. Bacterial abundance and production showed no differences at the high tide and low tide, and bacterial abundances were not different with depth, but bacterial production decreased with depth. Seasonal variation of bacterial abundance showed almost similar fluctuation pattern to those of DOC (dissolved organic carbon). HNF abundances ranged from 388 to 4,374 cells ml$^{-1}$ (average 1,344$\pm$130 cells ml$^{-1}$ ), were high in March, April, July and August. HNF abundance showed no difference between the high tide and low tide, and was not different with depth. The ingestion rates of HNF on bacteria were 1.0 to 6.3$\pm$10$^{6}$ bacteria 1$^{-1}$ h$^{-1}$ (average 3.12$\pm$0.55$\times$10$^{6}$ bacteria 1$^{-1}$ h$^{-1}$ ), resulting ingestion rates of HNF removed 19.4 to 141.4 %(average 62.3$\pm$12.0%) of bacterial production. Ingestion rates and grazing pressure of HNF on bacteria showed high correlation with HNF abundance. Although we cannot exactly discussion about seasonal variation of bacteria community in this study area where physical and chemical parameters were very complex, the results indicate that bacterial abundance and production were mainly controlled by resources supply as dissolved organic carbon and chlorophyll-a(bottom-up) except March which bacterial abundance and production uncoupled chlorophyll-a because of low dissolved organic carbon and low temperature, and were controlled by HNF grazing pressure(top-down) in the warm seasons except the winter.

Feeding behavior of the copepod Temora turbinata: clearance rate and prey preference on the diatom and microbial food web components in coastal area

  • Chang, Kwang-Hyeon;Doi, Hideyuki;Nishibe, Yuichiro;Nam, Gui-Sook;Nakano, Shin-Ichi
    • Journal of Ecology and Environment
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    • v.37 no.4
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    • pp.225-229
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    • 2014
  • Feeding behavior of Temora turbinata was investigated through laboratory experiments with special emphasis on its food preference and consequent clearance rate on diatom and microbial components given as common natural food assemblage of coastal area (Uchiumi, Uwa Sea, Japan). Among available prey items, T. turbinata showed the highest clearance rate for Thalassiosira spp. ($0.23{\pm}0.08L\;Temora^{-1}day^{-1}$) followed by Chaetoceros spp. ($0.11{\pm}0.03L\;Temora^{-1}day^{-1}$), but clearance rates for other diatom, Nitzschia spp. was lower (0.03 to $0.07L\;Temora^{-1}day^{-1}$). Bacterial abundances showed no response against 24-h feeding of T. turbinata. Feeding of T. turbinata on heterotrophic nanoflagellates (HNF) was apparent when clearance rates of T. turbinata on diatoms were relatively low, but T. turbinata did not consume HNF as well as ciliates with Thalassiosira spp. of which clearance rate was highest. The results suggest that HNF and ciliates are possible supplementary prey item for T. turbinata, but their contribution as food sources can be limited by the presence of other prey items such as preferable diatom species.

Synthesis and Crystallization of Hydrazinium Nitroformate(HNF) as Eco-friendly Oxidizer (친환경 산화제 HNF 합성 및 결정화 연구)

  • Kim, Jina;Kim, Min Jun;Min, Byoung Sun
    • Journal of the Korean Society of Propulsion Engineers
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    • v.19 no.4
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    • pp.69-76
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    • 2015
  • Recently, environmental sustainability of the transitional explosives and propellants is an issue of growing importance in energetic materials. For examples, ammonium perchlorate(AP) as an solid propellants oxidizer could create a poisonous gas and atmospheric pollutions, such as HCl. Among the several oxidizers, hydrazinium nitroformate(HNF) is an effective candidate substance for eco-friendly oxidizer, which has high density, pressure index, and less smog generating property during combustion for the Divert and Attitude Control System(DACS). This study was confirmed a synthesis through various conditions, was performed for the essential data of solubility the crystallization process. Also, crystallization process such as cooling, drowning-out and sonication were performed.