• Journal of Life Science
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• v.18 no.1
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• pp.120-128
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• 2008

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo1L is a cytokine that activates apoptosis through cell surface death receptors. TRAIL has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. Euphorbiae humifusae Wind has been used in traditional Oriental medicine as a folk remedy used for the treatment of cancer. However, the mechanism responsible for the anticancer effects of E. humifusae not clearly understood. Here, we show that treatment with subtoxic doses of water extract of E. humifusae (WEEH) in combination with TRAIL induces apoptosis in TRAIL-resistant human gastric carcinoma AGS cells. Combined treatment with WEEH and TRAIL induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly (ADP-ribose) polymerase. Combined treatment also triggered the loss of mitochondrial membrane potential. Furthermore, co-treatment with WEEH and TRAIL down-regulated the protein levels of the anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP and cIAP-1. Although more study will be needed to examine the detailed mechanisms, this combined treatment may offer an attractive strategy for safely treating gastric adenocarcinomas and the results provide important new insights into the possible molecular mechanisms of the anticancer activity of E. humifusae.

• Journal of Life Science
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• v.24 no.8
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• pp.820-826
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• 2014

The localization to specific subcellular sites and the regulation of cell surface receptors and channels are crucial for proper functioning. Postsynaptic density-95/Disks large/Zonula occludens-1 (PDZ)-domain is involved in recognition of and interaction between various proteins, by which the localization and the regulation are mediated. Multi-PDZ domain protein 1 (MUPP1) contains 13 PDZ domains. MUPP1 serves a scaffolding function for structure proteins and signaling proteins, but the mechanism how MUPP1 is stabilized and signalized has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and Parkin. Parkin is an E3 ubiquitin ligase. Loss-of-function mutations of Parkin gene are known to cause an autosomal recessive juvenile parkinsonism. Parkin bound to the $12^{th}$ PDZ domain, but not to other PDZ domains of MUPP1. The C-terminal end of Parkin has a type II PDZ-association motif, which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, Parkin co-localized with MUPP1. When co-expressed with ubiquitin in HEK-293T cells, MUPP1 has been strongly ubiquitinated by Parkin. These findings collectively suggest that MUPP1 is a novel substrate of Parkin and its function or stability could be modulated by Parkin-mediated ubiquitination.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.97-105
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• 1993

Adenosine receptors in rat adipose tissues have been reported to be of $A_{1}$ subclass, and their stimulation leads to inhibition of adenylyl cyclase, resulting in inhibition of lipolysis. In the present study we investigated changes in $A_{1}$ adenosine receptor-adenylyl cyclase system of adipocytes following induction of experimental diabetes in rats. One week following experimental diabetes were induced by intravenous injection of streptozotocin (50 mg/kg body wt.), adipocytes from rats $(170{\sim}230g)$ fed ad libitum were isolated using collagenase. When adipocytes were incubated for 1 h with 1 unit/ml adenosine deaminase and $1\;{\mu}M$ isoproterenol, and assayed for glycerol formation, it was found that the inhibition of lipolysis in diabetic adipocytes by $(-)-N^{6}-(R-phenylisopropyl)adenosine$ (PIA), an $A_{1}$, adenosine receptor agonist, was twice that of control adipocytes. In an effort to delineate the mechanism(s), $[^{3}H]PIA$ binding to adipocytic membranes from diabetic and control rats were determined. Neither the affinities nor numbers of $A_{1}$ adenosine receptor were significantly different from each other (Best fit parameters for the one-site model are: $K_{d}=0.51{\pm}0.09nM$ and $B_{max}=1.60{\pm}0.12\;pmoles/mg$ protein for control membranes; $K_{d}=0.54{\pm}0.21\;nM$ and $B_{max}=1.72{\pm}0.31\;pmoles/mg$ protein for diabetic membranes). However, the inhibiton by PIA of the isoproterenol-stimulated adenylyl cyclase activities was found to be 1.9 times higher in adipocytic membranes from diabetic rats than those from controls. These results suggest that the increased sensitivity of inhibition of lipolysis to PIA in adipocytic membranes from diabetic rats is due to changes in signal transduction pathways, rather than alterations of $A_{1}4 adenosine receptor molecules themselves.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1208-1214
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• 2011

Caffeine, a psychoactive stimulant, has been implicated in the modulation of learning and memory functions due to its action as a non-selective adenosine receptors antagonist. On the contrary, some side effects of caffeine have been reported, such as an increased energy loss and metabolic rate, decrease DNA synthesis in the spleen, and increased oxidative damage to exerted on LDL particles. Therefore, the aim of this study was to develop a safe stimulant from natural plants mixture (Aralia elata, Acori graminei Rhizoma, Chrysanthemum, Dandleion, Guarana, Shepherd's purse) that can be used as a substitute for caffeine. Thirty SD rats were divided into three groups; control group, caffeine group (15.0 mg/kg, i.p.), and natural plants mixture group (NP, 1 mL/kg, p.o.). The effect of NP extract on stimulant activity was evaluated with open-field test (OFT) and plus maze test for measurement of behavioral profiles. Plasma lipid profiles, lipid peroxidation in LDL (conjugated dienes), total antioxidant capacity (TRAP) and DNA damage in white blood, liver, and brain cells were measured. In the OFT, immobility time was increased significantly by acute (once) and chronic (3 weeks) supplementation of NP and showed a similar effect to caffeine treatment. Three weeks of caffeine treatment caused plasma lipid peroxidation and DNA damage in liver cells, whereas there were no changes in the NP group. NP group showed a higher plasma HDL cholesterol concentration compared to the caffeine group. The results indicate that the natural plants mixture had a stimulant effect without inducing oxidative stress.

• Journal of Ginseng Research
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• v.26 no.4
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• pp.178-186
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• 2002

The present study was attempted to investigate the effects of total ginseng saponin (G75), panaxadiol-type (PDS) and panaxatriol-type saponin (PTS) on contractile responses of vasoconstrictors in aortic smooth muscle stripes of normotensive (NR) and spontaneous hypertensive rats (SHR). Phenylephrine (an adrenergic $\alpha$$\_$1/-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in both NR and AHR aorta, respectively. Phenylephrine- and high potassium-induced contractile responses were greater in NA than those in SHR aortic smooth muscle stripes. In NR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and PTS (300 $\mu$g/ml), respectively whereas phenylephrine (10$\^$-6/ M)-induced contractile responses were markedly inhibited. In SHR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and moderate doses of PTS (150-300 $\mu$g/ml), respectively but greatly blocked by high concentration of PTS (600 $\mu$g/ml). Phenylephrine (10$\^$-6/ M)-induced contractile responses were inhibited in a dose dependent fashion (150-600 $\mu$g/ml) by the pretreatment with PTS while not altered in the presence of GTS (300 $\mu$g/ml) and PDS (300 $\mu$g/ml), respectively. Taken together, these experimental results suggest that ginseng saponins cause vascular relaxation through blockade of adrenergic $\alpha$$\_$1/-receptors and some unknown mechanisms, and that there is some difference in sensitivity of vascular smooth muscle between NR and SHR in responses to ginseng saponins. It seems that panaxatriol type of some ginseng saponins has the greatest potency in vascular relaxation.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.304-310
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• 1999

Background: IFN-$\gamma$ plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-$\gamma$ caused by a defective IFN-$\gamma$ receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-$\gamma$ in the development of chronic refractory tuberculosis. Methods: The LPS-induced TNF-$\alpha$ production with or without IFN-$\gamma$ priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-$\gamma$ receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-$\gamma$ is related to IFN-$\gamma$ receptor deficiency or not. Results: The ratio of TNF-$\alpha$ produced in response to stimulation with INF-$\gamma$ and LPS to LPS alone was $13.5{\pm}7.6$ in controls, $10.8{\pm}6.4$ in recently diagnosed tuberculosis patients and $6.7{\pm}3.9$ in chronic refractory tuberculosis patients. The priming effect of IFN-$\gamma$ significantly decreased in chronic refractory tuberculosis patients compared with that in controls(p=0.002). However, IFN-$\gamma$ receptor deficiency was detected in one of chronic refractory tuberculosis patients. Conclusion: The decrease of the priming effect of IFN-$\gamma$ may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-$\gamma$ receptor deficiency.

• Korean journal of applied entomology
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• v.49 no.4
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• pp.277-287
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• 2010

Several species of the genus Aphidius are used in biological control programs against aphid pests throughout the world and their behavior and physiology are well studied. While the importance of sensory organs in their behavior is understood, their antennal structure remains largely unknown. In this study, the external morphology and distribution of the antennal sensilla on the antennal of both female and male adults of A. colemani were described using scanning electron microscopy (SEM). Generally, the filiform antennae of males ($l,515.2{\pm}116.5\;{\mu}m$) are longer than females ($l,275.1{\pm}103.4\;{\mu}m$). Antennae of this species are made up of radicle, scape, pedicel and flagellomeres. Male and female antennae differed in the total number of flagellomeres as 15 in males and 13 in females. The result of SEM observation was characterization and grouping of seven types of receptors into morphological classcs: Bohm bristles, Sensilla placodea, 2 types of S. coeloconica and S. trichodea, and S. basiconica as with a tip pore and with wall pores. In addition, the possible functions of the above sensilla types arc discussed in light of previously published literature; mechanoreception (Bohm bristles, S, coeloconica I & II and S. trichodea) and chemoreception (S. placodea, S. basiconica type I & II).

• Korean Journal of Biological Psychiatry
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• v.14 no.3
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• pp.167-176
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• 2007

Objectives:A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). Methods:We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. Results:Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. Conclusion:These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polym- orphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.181-190
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• 2007

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1065-1072
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• 2004

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.