• Title/Summary/Keyword: Binding protein

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DEVELOPMENTAL PSYCHOPHARMACOLOGY - DEVELOPMENTAL PHARMACOKINETICS, PHARMACODYNAMICS AND PHARMACOGENETICS - (발달학적 정신약물학 - 발달학적 약동학, 약역학 및 약물유전학 -)

  • Cho, Soo-Churl
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.14 no.2
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    • pp.157-173
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    • 2003
  • The history of pediatric psychopharmacology is very short and the research on safety, efficacy and side effects is preliminary and long-term effect on growth and maturation is not well known yet. Clinical findings have shown that the responses to antidepressants, antipsychotics, CNS stimulants and steroids in children and adolescents might be different from adult populations. Based on these findings, this paper reviewed three issues, Firstly, in developmental pharmacokinetics. the author discussed the developmental factors affecting drug absorption, distribution, protein-binding, metabolism and excretion. Secondly, in developmental pharmacodynamics, developmental characteristics of dopamine, serotonin, norepinephrine receptors and their clinical implications were reviewed. Lastly, in pharamcogenetic part, the clinical utility of pharmacogenetics, pharmacokinetic aspects of pharmacogenetics, the pharmacodynamic aspects of pharmacogenetics, the association studies of dopamine-related alleles in neuropsychiatric disorders such as attention-deficit hyperactivity disorders or Tourette’s disorders, pharmacogenetic studies dopamine-related alleles and the pharmacogenetic studies of serotonin-related alleles. Based on these preliminary research, future pharmacogenetic applications in childhood and adolescent psychiatry were also discussed.

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The Mechanism of LDL Receptor Up-regulation by Ginsenoside-Rb2 in HepG2 Cultured under Enriched Cholesterol Condition (고콜레스테롤 조건하에 배양된 HepG2에서의 ginsenoside-Rb2에 의한 LDL receptor 억제 완화 기전)

  • Lim, G-Rewo;Lee, Hyun-Il;Kim, Eun-Ju;Ro, Young-Tae;Noh, Yun-Hee;Koo, Ja-Hyun
    • Journal of Ginseng Research
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    • v.28 no.2
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    • pp.87-93
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    • 2004
  • The effect of ginsenoside-Rb2, one of a major pharmacological component of Panax ginseng C.A. Meyer, on low density lipoprotein (LDL) receptor expression was investigated and compared with hypocholesterolemic drug lovastatin. In HepG2 cell, exogenous cholesterol decreased LDL receptor mRNA expression, but ginsenoside-Rb2 recovered this reduction of LDL receptor mRNA up to normal expression level. Lovastatin also increased LDL receptor mRNA expression as similar as ginsenoside-Rb2 did. The reduction of sterol regulatory element binding protein (SREBP) transcription by exogenous cholesterol was also similarly recovered by ginsenoside-Rb2 and lovastatin addition. Compound K, a metabolite of ginsenoside-Rb2 and -Rb1 by human intestinal bacteria also increased the SREBP mRNA expression in cholesterol-enriched condition. Ginsenoside-Rb2 seems to up-regulate LDL receptor mRNA expression through the induction of de novo SREBP transcription. Therefore, increased expression of SREBP mRNA by ginsenoside-Rb2 elevated the LDL receptor mRNA expression in HepG2 cells, and these inductions possibly drop the plasma cholesterol level in hypercholesterolemia patients, in vivo, as likely in case of lovastatin.

Black ginseng extract ameliorates hypercholesterolemia in rats

  • Saba, Evelyn;Jeon, Bo Ra;Jeong, Da-Hye;Lee, Kija;Goo, Youn-Kyoung;Kim, Seung-Hyung;Sung, Chang-Keun;Roh, Seong-Soo;Kim, Sung Dae;Kim, Hyun-Kyoung;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.40 no.2
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    • pp.160-168
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    • 2016
  • Background: Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Methods: Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. Results: We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

Miscanthus EST-originated Transcription Factor WRKY Expression in Response to Low Temperature in Warm-season Turfgrasses (억새 EST 정보 유래 전사요소 WRKY의 난지형 잔디의 저온 발현 반응성)

  • Chung, Sung Jin;Choi, Young In;Lee, Geung-Joo
    • Weed & Turfgrass Science
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    • v.2 no.4
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    • pp.368-375
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    • 2013
  • Whole genome transcriptomes from Miscanthus species were sequenced and analyzed, which provided 50 different types of transcription factor (TF) involving various developmental processes or environmental stresses. Among the explored TF, WRKY gene family was the major type and one of the WRKY genes, MSIR7180_WRKY4, induced under low temperature environment was selected to investigate how the Miscanthus-originated MSIR7180_WRKY4 TF responds when exposed to low temperature in four warm-season turfgrasses (Z. matrella 'Semil', bermudagrass, St. Augustinegrass, and seashore paspalum). The MSIR7180_WRKY4 was expressed higher during low temperature period in Bermudagrass, but the expression was enhanced in St. Augustinegrass. In contrast, the gene in 'Semil' cultivar was barely expressed and relatively less expressed, but repressed gradually in seashore paspalum, which seems to allow two turfgrasses stay-green longer in the fall season. The results indicate that bermudagrass and St. Augustinegrass adapt to low temperature quickly, but relative tolerance to low or cold temperature at the molecular level needs to be further investigated at different physiological stages and the corresponding genes systematically.

The Association between A-FABP Promoter Genotype and Carcass Traits in Pigs (비육돈의 도체형질과 A-FABP Promoter 유전자형의 연관 분석)

  • Han, Sang-Hyun;Cho, In-Cheol;Lee, Chong-Eon;Ko, Moon-Suck;Seong, Pil-Nam;Park, Beom-Young
    • Food Science of Animal Resources
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    • v.27 no.3
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    • pp.382-386
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    • 2007
  • The association between the promoter region genotypes of the porcine adipocyte fatty acid binding protein (A-FABP) gene and carcass traits in commercial pigs was examined. Interestingly, only two different genotypes (-406T/T and T/C) for the A-FABP gene were detected using Hinf-RFLP for the substitution mutation T-406C in the A-FABP promoter in commercial pigs, and no -406C/C homozygotes were detected. The reason for the lack of the -406 C/C genotype is due to the breeding system in which only Duroc, which has a high frequency of -406C/- in this locus among the three breeds involved in commercial pig production, is typically used as a terminal sire. The pigs containing the genotype -406C/- were significantly associated with an increase in intramuscula. fat content and carcass weight (p<0.05), but there was no association with the other carcass traits tested (fat composition, color score, texture score, moisture, and separation score between muscles). This study suggests that the -406C/- genotype of the porcine A-FABP gene may not only be a useful molecular marker for intramuscular fat, but may also contribute to the improvement of meat quality by the production of well-marbled pigs by breeding animals containing this genotype, especially Duroc, as a terminal sire for commercial pigs.

Antiobesity Effect of the Bacillus subtilis KC-3 Fermented Soymilk in 3T3-L1 Adipocytes (3T3-L1 지방세포에서 Bacillus subtilis KC-3 발효두유의 항비만 효과)

  • Kim, Ji-Young;Jeong, Jung-Eun;Moon, Suk-Hee;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.8
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    • pp.1126-1131
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    • 2010
  • The antiobesity effect of soymilks fermented with Bacillus subtilis KC-3 (KCCM 42923) from cheonggukjang was compared with other sources of B. subtilis KCCM 11316 and B. subtilis MYCO. The antiobesity effect was investigated by measuring the release of leptin, Oil red O staining, glycerol secretions and adipogenic transcription factor by reverse transcription-polymerase chain reaction (RT-PCR) in the 3T3-L1 adipocytes. Fermented soymilk with B. subtilis KC-3 (F-KC) led to decrease levels of leptin secretion and increase levels of glycerol secretion in the cells. In addition, F-KC reduced contents of Oil red O dye in the 3T3-L1 adipocytes. Also, mRNA expression levels of both SREBP-1c (sterol regulatory element-binding protein 1-c) and PPAR-$\gamma$ (peroxisome proliferator-activated receptor-$\gamma$), which are adipogenic transcription factor, in cells treated with F-KC were markedly down regulated. These results demonstrate that the Bacillus subtillis fermented soymilk (F-KC) decreased lipid content in 3T3-L1 adipocytes by inhibiting lipogenesis. All B. subtilis fermented soymilks had shown antiobesity activities, however, F-KC exhibited the strongest antiobesity effect in the 3T3-L1 adipocytes. Our study suggests that especially F-KC increased the potential of antiobesity effects.

Identification of Single Nucleotide Polymorphism of H-FABP Gene and Its Association with Fatness Traits in Chickens

  • Wang, Yan;Shu, Dingming;Li, Liang;Qu, Hao;Yang, Chunfen;Zhu, Qing
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.12
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    • pp.1812-1819
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    • 2007
  • Heart fatty acid-binding protein gene (H-FABP) is an important candidate gene for meat quality. One of the objectives of this study was to screen single nucleotide polymorphisms (SNP) of chicken H-FABP gene among 252 individuals that included 4 Chinese domestic chicken breeds (Fengkai Xinghua (T04), Huiyang Huxu (H), Qingyuan Ma (Q), Guangxi Xiayan (S1)), 2 breeds developed by the Institute of Animal Science, Guangdong Academy of Agricultural Sciences (Lingnan Huang (DC), dwarf chicken (E4)) and one introduced broiler (Abor Acre (AA)). Another objective of this study was to analyze the associations between polymorphisms of the H-FABP gene and fat deposition traits in chickens. PCR-SSCP was used to analyze SNPs in H-FABP and 4 SNPs (T260C, G675A, C783T and G2778A) were detected. Associations between polymorphic loci and intramuscular fat (IMF), abdominal fat weight (AFW) and abdominal fat percentage (AFP) were analyzed by ANCOVA method. The results showed that the T260C genotypes were significantly associated with IMF (p = 0.0233) and AFP (p = 0.0001); the G675A genotypes were significantly associated with AFW, AFP (p<0.01) and IMF (p<0.05); at the C783T locus, AFW and AFP differed highly between genotypes. However, the G2778A loci did not show any significant effect on fat deposition traits in this study. In addition, we found that there were some differences between AFP and definite haplotypes through a nonparametric statistical method, so the haplotypes based on the SNPs except G2778A loci were also significantly associated with IMF, AFW (g) (p<0.05) and AFP (%) (p<0.001). Significantly and suggestively dominant effects of H4H4 haplotype were observed for IMF and the H2H3 was dominant for AFW (g) and AFP (%). The results also revealed that H5H7 haplotype had a negative effect on IMF, while the H5H6 had a positive effect on AFW (g) and AFP (%).

Investigation of the Insulin-like Growth Factor System in Breast Muscle during Embryonic and Postnatal Development in Langshan and Arbor Acres Chickens Subjected to Different Feeding Regimens

  • Lu, F.Z.;Chen, J.;Wang, X.X.;Liu, Honglin
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.4
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    • pp.471-482
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    • 2009
  • Nutrient availability may control muscle growth directly and indirectly through its influence on regulatory factors. We analyzed the effects of nutrient availability on the breast muscle insulin-like growth factor system. Real time RT-PCR was used to quantify the level of transcription in breast muscle from Langshan (LS) layer and Arbor Acres (AA) broiler chickens subjected to different feeding regimens during embryonic and postnatal development. The AA chickens were fed AA diet (AA, control group) while the LS chickens were either fed LS diet (LL) or AA diet (LA). According to our results, insulin-like growth factor (IGF)-II (embryonic day 16 (E16) - postnatal day 42 (P42)), IGF-I receptor (IGF-IR, E18-P42), and IGF binding protein (IGFBP)-2 (E18-P42), -5 (E16-P14), -7 (E12-P0), and -3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I. In comparison, IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E14-P0), and IGFBP-3 (E16-P0) were positively correlated with IGF-II, while IGF-IR (E10-E16) and IGFBP-3 (P0-P28) were negatively correlated with IGF-II. Moreover, IGFBP-2 (E16-P42), -7 (E10-E16), and -3 (E10-E16) were positively correlated with IGF-IR, while IGFBP-3 (P0-P28) was negatively correlated with IGF-IR. Finally, IGFBP-7 (E12-P0) was positively correlated with IGFBP-3, while IGFBP-2 (P0-P28) and -7 (P0-P42) were negatively correlated with IGFBP-3. Overall, the AA chickens exhibited higher levels of IGF-I, IGF-IR, and IGFBP-2 mRNA expression than the LL chickens, while the opposite was true for IGFBP-7. No strain differences in IGF-I, IGF-IR, and IGFBP-7 mRNA expression were detected between LA and AA chickens; however, a strain difference was observed for IGFBP-2. LA chickens exhibited higher levels of IGFBP-2 than LL chickens, while the opposite was true for IGFBP-7. Our data show the first evidence that certain genes may be correlated during specific developmental periods and that strain differences in the expression of those genes in LS and AA chickens are due to differential responses to the same diet.

[ $P2X_2$ ] Receptor Activation Potentiates PC12 Cell Differentiation Induced by ACAP in Acidic Environments

  • Lee, Myung-Hoon;Nam, Jin-Sik;Ryu, Hye-Myung;Yoo, Min;Lee, Moon-Hee
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.197-206
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    • 2007
  • P2X receptors are membrane-bound ion channels that conduct $Na^+,\;K^+$, and $Ca^{2+}$ in response to ATP and its analogs. There are seven subunits identified so far ($P2X_1-P2X_7$). $P2X_2$ receptors are known to be expressed in a wide range of organs including brains and adrenal grands. PC12 cells are originated from adrenal grand and differentiated by nerve growth factor or pituitary adenylate cyclase activating poly peptide (PACAP). Previous studies indicate that $P2X_2$ receptor activation in PC12 cells couples to $Ca^{2+}-dependent$ release of catecholamine and ATP. It is known that acidic pH potentiates ATP currents at $P2X_2$ receptors. This leads to a hypothesis that $P2X_2$ receptors may play an important role in PC12 cell differentiation, one of the characteristics of which is neurite outgrowth, induced by the hormones under lower pH. In the present study, we isolated several clones which potentiate neurite outgrowth by PACAP in acidic pH (6.8), but not in alkaline pH (7.6). RT-PCR and electrophysiology data indicate that these clones express only functional $P2X_2$ receptors in the absence or presence of PACAP for 3 days. Potentiation of neurite outgrowth resulted from PACAP (100 nM) in acidic pH is inhibited by the two P2X receptor antagonists, suramin and PPADS ($100\;{\mu}M)$ each), and exogenous exprerssion of ATP-binding mutant $P2X_2$ receptor subunit ($P2X_2[K69A]$). However, acid sensing ion channels (ASICs) are not involved in PACAP-induced neurite outgrowth potentiation in lower pH since treatments of an inhibitor of ASICs, amyloride ($10\;{\mu}M$), did not give any effects to neurite extension. The vesicular proton pump ($H^+-ATPase$) inhibitor, bafilomycin (100 nM), reduced neurite extension indicating that ATP release resulted from $P2X_2$ receptor activation in PC12 cells is needed for neurite outgrowth. These were confirmed by activation of mitogen activated protein kinases, such as ERKs and p38. These results suggest roles of ATP and $P2X_2$ receptors in hormone-induced cell differentiation or neuronal synaptogenesis in local acidic environments.

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Lack of Associations between Vitamin D Metabolism-Related Gene Variants and Risk of Colorectal Cancer

  • Mahmoudi, Touraj;Karimi, Khatoon;Arkani, Maral;Farahani, Hamid;Nobakht, Hossein;Dabiri, Reza;Asadi, Asadollah;Vahedi, Mohsen;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.957-961
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    • 2014
  • Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluated genetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1). Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled in this case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results: In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRC and the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants and CRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC, and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledge has not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesis need to be further investigated.