• Nutrition Research and Practice
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• v.6 no.4
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• pp.322-327
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• 2012

This study investigated the hypothesis that a sorghum extract exerts anti-diabetic effects through a mechanism that improves insulin sensitivity via peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$) from adipose tissue. Seven C57BL/6 mice were fed an AIN-93M diet with fat consisting of 10% of total energy intake (LF) for 14 weeks, and 21 mice were fed a high-fat AIN diet with 60% of calories derived from fat (HF). From week 8, the HF diet-fed mice were orally administered either saline (HF group), 0.5% (0.5% SE group), or 1% sorghum extract (1% SE group) for 6 weeks (n = 7/group). Perirenal fat content was significantly lower in the 0.5% SE and 1% SE groups than that in the HF mice. Levels of total and low-density lipoprotein cholesterol, triglycerides, glucose, and the area under the curve for glucose were significantly lower in mice administered 0.5% SE and 1% SE than those in HF mice. Serum insulin level was significantly lower in mice administered 1% SE than that in HF mice or those given 0.5% SE. PPAR-${\gamma}$ expression was significantly higher, whereas the expression of tumor necrosis factor-${\alpha}$ was significantly lower in mice given 1% SE compared to those in the HF mice. Adiponectin expression was also significantly higher in mice given 0.5% SE and 1% SE than that in the HF mice. These results suggest that the hypoglycemic effect of SE may be related with the regulation of PPAR-${\gamma}$-mediated metabolism in this mouse model.

• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.254-259
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• 2011

Objectives The aim of this study was to assess variations in caudate volume according to dopamin receptor D2/ankyin repeat and kinase domain containing 1 (DRD2/ANKK1) Taq 1a polymorphisms in young healthy adults and to evaluate the relationship between caudate volumes and psychiatric symptoms as measured by the Brief Psychiatric Rating Scale. Methods Genetic information regarding DRD2/ANKK1 Taq 1a and T1-weighted brain magnetic resonance images were acquired from 30 young healthy adults. Automatic segmentation of caudate was performed using the FreeSurfer program. Results Individuals with A2 homozygotes of DRD2/ANKK1 Taq 1a polymorphisms (n = 10) had greater right caudate volumes compared to those with A1 allele (s)(18.4% greater ; p = 0.019). Right caudate volumes were negatively associated with total scores of the Brief Psychiatric Rating Scale (${\beta}$=-0.50 ; p = 0.016). Conclusions Our findings suggest the possibility that DRD2/ANKK1 Taq 1a polymorphisms may underlie the psychiatric symptoms by influencing the structure of the right caudate.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.258-267
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• 2001

Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

• Parasites, Hosts and Diseases
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• v.46 no.4
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• pp.209-216
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• 2008

A monoclonal antibody against Toxoplasma gondii of Tg556 clone (Tg556) blotted a 29 kDa protein, which was localized in the dense granules of tachyzoites and secreted into the parasitophorous vacuolar membrane (PVM) after infection to host cells. A cDNA fragment encoding the protein was obtained by screening a T. gondii cDNA expression library with Tg556, and the full-length was completed by 5'-RACE of 2,086 bp containing an open reading frame (ORF) of 669 bp. The ORF encoded a polypeptide of 222 amino acids homologous to the revised GRA3 but not to the first reported one. The polypeptide has 3 hydrophobic moieties of an N-terminal stop transfer sequence and 2 transmembrane domains (TMD) in posterior half of the sequence, a cytoplasmic localization motif after the second TMD and an endoplasmic reticulum (ER) retrival motif in the C-terminal end, which suggests GRA3 as a type III transmembrane protein. With the ORF of GRA3, yeast two-hybrid assay was performed in HeLa cDNA expression library, which resulted in the interaction of GRA3 with calcium modulating ligand (CAMLG), a type II transmembrane protein of ER. The specific binding of GRA3 and CAMLG was confirmed by glutathione S-transferase (GST) pull-down and immunoprecipitation assays. The localities of fluorescence transfectionally expressed from GRA3 and CAMLG plasmids were overlapped completely in HeLa cell cytoplasm. In immunofluorescence assay, GRA3 and CAMLG were shown to be co-localized in the PVM of host cells. Structural binding of PVM-inserted GRA3 to CAMLG of ER suggested the receptor-ligand of ER recruitment to PVM during the parasitism of T. gondii.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2012.11a
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• pp.4-4
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• 2012

Proteins enable biology to be viable through molecular interactions (such as in antigen-antibody, ligand-receptor, and drug-target) with

• Environmental Mutagens and Carcinogens
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• v.24 no.4
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• pp.163-170
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• 2004

CYP1B1 enzyme metabolize PAHs and estradiol. CYP1B1 metabolize estradiol to 4-hydroxyestradiol that is considered as carcinogenic metabolite. Luciferase activity was induced about 20 folds over that control by 1 nM TCDD (2,3,7,8-tetrchlorodibenzo-p-dioxin) and these inductions were dose-dependent. Recent industrialized society, human hasbeen widely been exposed to widespread environmental contaminants such as PAHs (polycyclic aromatic hydrocarbon) that are originated from the incomplete combustion of hydrocarbons. PAHs are known to be ligands of the AhR (aryl hydrocarbon receptor). Induction of cytochrome P4501B1(CYP1B1) in cell culture is widely used as a biomarket for PAHs. Therefore we have studied the effect of PAHs in the human breast cancer cells MCF-7 to evaluate bioactivity of PAHs. Cytochrome P4501B1(CYP1B1) is known to be inducible by xenobiotic compounda such as policyclic aromatic hydrocarbon (PAH) and dioxins such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). And these induction of CYP1B1 is also regulated by many categories of chemicals. In order to investigate the effects of several chemicals on CYP1B1 gene expression in luciferase gene, and then transfected into these cells. After treatment of chemicals, the luciferase activity was measured. We examined effects of PAHs on the CYP1B1-lucifrease reporter gene and CYP1B1 mRNA level. Benzo(k)fluoranthene showed strong response to CYP1B1 promoter activity stimulation, and also CYP1B1 mRNAs increase in MCF-7 cells in a concentration-dependent manner. flvonoids such as genistein decreased B(k)F induced luciferase activity at low concentration. it exhibited stimulatory effect at high concentration.

• The Korea Journal of Herbology
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• v.37 no.4
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• pp.17-29
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• 2022

Objective : The present study comparatively analyzed the anti-obesity effect of Arctium lappa L. roots with and without microwave processing. Methods : Four HFD groups except for the Normal group (n=8) were allocated: Control, microwave-processed dried Arctium lappa L. roots (MAL) extract 400 mg/kg/d (MAL400), MAL extract 800 mg/kg/d (MAL800), and the dried Arctium lappa L. roots (DAL) extract 800 mg/kg/d (DAL800). The efficacy of MAL and DAL was confirmed in terms of the serum biochemical index, protein expressions related to the synthesis of triglyceride (TG) and total cholesterol (TC) and 𝛽-oxidation, and histopathological staining. Results : Both MAL and DAL treatments significantly reduced final body weight and body weight gain. MAL800 treatment significantly reduced serum TG, TC, low-density lipoprotein cholesterol, and leptin levels, but the serum high-density lipoprotein cholesterol and adiponectin concentrations were dramatically increased. In particular, leptin in the MAL800 group was reduced by 14.1% compared with the DAL800 group. Moreover, the MAL800 treatment showed an effect superior to the DAL800 treatment in the reduction of serum TC, the sirtuin 1 (Sirt1) activation, and the inhibition of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) gene expression. In particular, unlike the DAL800 treatment, MAL treatment significantly led to the activation of peroxisome proliferator-activated receptor alpha (PPAR𝛼). Subsequently, PPAR𝛼 meaningfully regulated downstream proteins associated with 𝛽-oxidation. Conclusion : These findings suggest that Arctium lappa L. roots with microwave processing effectively ameliorate obesity through the regulation of leptin and TC and the promotion of 𝛽-oxidation compared with Arctium lappa L. roots without microwave processing.

• Toxicological Research
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• v.8 no.2
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• pp.343-357
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• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.93-101
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• 1988

Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and $EC_{50}=0.52\;{\mu}M$ of intact endothelial rings was about 2 times greater than $EC_{50}=0.28\;{\mu}M$ of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and the $IC_{50s}$ were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The $IC_{50}$ of oxybutynin on the KCl-induced contraction was $49.7\;{\mu}M$. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with $IC_{50}$ of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with $IC_{50}$ of oxybutynin $(49.7\;{\mu}M$). Oxybutynin inhibited $0.1\;{\mu}M$ Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but $35\;{\mu}M$ histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration $(5{\times}10^{-4}M)$ of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.43-49
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• 2008

Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry. The hippocampal neurons were used between 10 and 13 days in culture from embryonic day 18 rats. Pretreatment of the cells with apigenin ($1{\mu}M$ to $100{\mu}M$) for 5 min inhibited glutamate ($100{\mu}M$, 1 min) induced $[Ca^{2+}]_i$ increase, concentration-dependently. Pretreatment with apigenin ($30{\mu}M$) for 5 min significantly decreased the $[Ca^{2+}]_i$ responses induced by two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, $10{\mu}M$, 1 min) and N-methyl-D-aspartate (NMDA, $100{\mu}M$, 1 min), and significantly inhibited the AMPA-induced peak currents. Treatment with apigenin also significantly inhibited the $[Ca^{2+}]_i$ response induced by 50 mM KCl solution, decreased the $[Ca^{2+}]_i$ responses induced by the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxy-phenylglycine (DHPG, 100 $[Ca^{2+}]_i$, 90 s), and inhibited the caffeine (10 mM, 2 min)-induced $[Ca^{2+}]_i$ responses. Furthermore, treatment with apigenin ($30{\mu}M$) significantly inhibited the amplitude and frequency of 0.1 mM $[Mg^{2+}]_o$-induced $[Ca^{2+}]_i$ spikes. These data together suggest that apigenin inhibits glutamate-induced calcium signaling in cultured rat hippocampal neurons.