• Title/Summary/Keyword: modulatory

Search Result 277, Processing Time 0.026 seconds

Short Heterodimer Partner as a Regulator in OxLDL-induced Signaling Pathway

  • Kimpak, Young-Mi
    • Proceedings of the PSK Conference
    • /
    • 2001.10a
    • /
    • pp.109-113
    • /
    • 2001
  • Oxidized low-density lipoprotein (oxLDL) has been shown to modulate transactivations by the peroxisome proliferator activated receptor (PPAR)$\gamma$ and nuclear factor-kappa B (NF$\kappa$B). In this study, the oxLDL signaling pathways involved with the NF$\kappa$B transactivation were investigated by utilizing a reporter construct driven by three upstream NF$\kappa$B binding sites, and various pharmacological inhibitors. OxLDL and its constituent lysophophatidylcholine (lysoPC) induced a rapid and transient increase of intracellular calcium and stimulated the NF-KB transactivation in resting RAW264.7 macrophage cells in an oxidation-dependent manner. The NF$\kappa$B activation by oxLDL or lysoPC was inhibited by protein kinase C inhibitors or an intracellular calcium chelator. Tyrosine kinase or PI3 kinase inhibitors did not block the NF$\kappa$B transactivation. Furthermore, the oxLDL-induced NF$\kappa$B activity was abolished by the PPAR$\gamma$ ligands. When the endocytosis of oxLDL was blocked by cytochalasin B, the NF$\kappa$B transactivation by oxLDL was synergistically increased, while PPAR transactivation was blocked. These results suggest that oxLDL activates NF-$\kappa$B in resting macrophages via protein kinase C- and/or calcium-dependent pathways, which does not involve the endocytic processing of oxLDL. The endocytosis-dependent PPAR$\gamma$ activation by oxLDL may function as an inactivation route of the oxLDL induced NF$\kappa$B signal. Short heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA-binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but suppressed by oxLDL and its constituent I3-HODE, a ligand for peroxisome proliferator-activated receptor y. Furthermore, SHP acted as a transcription coactivator of nuclear factor-$\kappa$B (NF$\kappa$B) and was essential for the previously described NF$\kappa$B transactivation by lysoPC, one of the oxLDL constituents. Accordingly, NF$\kappa$B, transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells, as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF$\kappa$B in oxLDL-treated, resting macrophage cells.

  • PDF

Zygotic Expression of c-myc Gene in Mouse Early Embryos: Functional Role of c-myc Promoter (생쥐 초기배아에서 c-myc Proto-Oncogene Promoter의 기능적 활성화)

  • Park, Ki-Soo;Kang, Hae-Mook;Shim, Chan-seob;Sun, Woong;Kim, Jae-man;Lee, Young-Ki;Kim, Kyung-jin
    • The Korean Journal of Zoology
    • /
    • v.38 no.4
    • /
    • pp.550-556
    • /
    • 1995
  • The c-myc proto-oncogene is Involved In the control of normal cell proliferation and differentiation of many cell lineages. Although it has heen suggested that c-myc may play an important role in the mammalian early development, it Is unclear whether the embryonic c-myc mRNA is originated from zygotic gene expression or stored maternal message. Thus, we have construded expression vectors, In which the 5, flanking sequences including c-myc promoter region and a large non-coding exon I are fused 'sith E. coli lacZ gene that encedes $\beta$-galactosldase as a reporter. As c-myc exon I contains a modulatory sequence, we designed t, vo types of vectors (pcmyc.Gall and pcmyc-Ga12) to examine the role of exon I in c-myc expression. The former contains the complete exon I and the later has a deletion in 40 bp of modulator sequence located In the exon I of c-myc These vectors were microInjected into fertilized one-cell embryos and $\beta$-galactosidase activity was examined by X-gal staining during early embryogenesis. $\beta$-galactosidase activity derived from c-myc promoter was decreased at two-cell stage. The expression level directed by pcmyc- Ga12 was similar to that of pcmyc-Gal1, indicating that the medulatory sequence in exon I may not be Involved at least In the regulation of embryonic c-myc expression. In summary, the present study indicates that the c-myc promoter is functional at the early stage embryo, and the regulation of c-myc expression is under the control of "zygotic" clock of preimplantation mouse embryos.e embryos.

  • PDF

Effect of the bee venom aqua-acupuncture on the neuronal activities of serotonergic system in brainstem (봉독약침자극(蜂毒藥鍼刺戟)이 뇌간(腦幹) 신경세포(神經細胞)와 Serotonin성(性) 신경세포(神經細胞)의 활성변화(活性變化)에 미치는 영향)

  • Kim, Hye-Nam;Koh, Hyung-Kyun;Park, Dong-Suk;Kang, Sung-Keel;Kim, Yong-Suk;Choi, Yong-Tae
    • Journal of Acupuncture Research
    • /
    • v.17 no.2
    • /
    • pp.119-138
    • /
    • 2000
  • This study was designed to evaluate the effect of the bee venom(BV) aqua-acupuncture on the neuronal activities of serotonergic(5-HT) system in the brainstem. After the BV aqua-acupuncture was applied on Chok-Samni(ST36) and the gluteal part(Blank locus) in rats, the number of Fos immunoreactive neurons was counted by using computerized image analyzing system. Also, the number of colocalization between 5-HT containing neurons Fos immunoreactive neurons were analyzed by using the double immunohistochemical technique. The results of the experiments were summarized as follows : 1. In almost every neucli, the Chok-Samni group and Blank locus group showed more increase in the number of Fos immunoreactive neurons than the control group. Especially, in Arc, DR, LC, RMg, Gi, PAG Rost and PAG LV, the Chok-Samni group showed more significant increase than the control group. Also, in PAG LV Mid and Arc, Chok-Samni group showed more significant increase than the Blank locus group. 2. In DR and PAG LV Mid, Chok-Samni group and the Blank locus group showed more significant increase in the number of colocalization between 5-HT containing neurons and Fos immunoreactive neurons than the control group after the BV aqua- acupuncture. Also, the Chok-Samni group showed more significant increase than the Blank locus group. Consequently, the BV aqua-acupuncture increased more potent the number of Fos immunoreactive neurons and the activity of serotonergic neurons. Furthermore, the BV aqua-acupuncture was more effective on Chok-Samni than Blank locus group. These results indicate that the BV aqua-acupuncture is very effective therapy to control pain. The therapeutic effect of BV aqua-acupunture may associated with the endogenous modulatory system such as serotonin Those data from the study can be applied to establish the effective treatment of the BV for pain control in the clinical field.

  • PDF

Influence of the Epithelium on the Contraction of Guinea Pig Isolated Tracheal Smooth Muscle (Guinea Pig 기도상피세포가 기도 평활근 수축에 미치는 영향)

  • Kwon, O.J.;Cho, S.H.;Park, I.W.;Kim, Y.W.;Han, S.K.;Shim, Y.S.;Kim, K.Y.;Han, Y.C.;Seoh, S.H.;Kim, K.W.
    • Tuberculosis and Respiratory Diseases
    • /
    • v.38 no.1
    • /
    • pp.8-15
    • /
    • 1991
  • It has been well known that the integrity of airway epithelium is important in development of bronchial hyperreactivity and bronchial asthma. But the mechanisms involved are still unclear. To evaluate that airway epithelium is able to modulate the contraction of guinea pig tracheal smooth muscle, we investigated the responsiveness of intact and epithelium-denuded tracheal strips to histamine and acetylcholine. And to evaluate whether cyclooxgenase products play a role in this modulatory mechanism, we also investigated the effect of indomethacin pretreatment on the tracheal responsiveness to histamine. Results were as follows: 1) In guinea pig tracheal smooth muscle the presence of airway epithelium significantly reduced the response to histamine. 2) In the presence of indomethacin dose-response curves and $EC_{50}$ values were similar between intact and epithelium-denuded tracheal strips, that is, indomethacin abolished the influence of epithelium on the contracion of tracheal smooth muscle. 3) The response of tracheal smooth muscle to acetylcholine was similar both in the presence and absence of epithelium. These results suggest that airway epithelium of guinea pig may generate an inhibitory signal to decrease the response of tracheal smooth muscle to histamine and cyclooxygenase products may contrbute to the modulation of airway epithelium on the contracion of tracheal smooth muscle.

  • PDF

Inhibitive Effect of Mouse Sarcoma 180 by Crude Polysaccharide Extracted from Fruiting Body of Aramillaria mellea (뽕나무버섯(Armillaria mellea)의 자실체에서 추출한 조다당류가 생쥐의 Sarcoma 180에 미치는 억제효과)

  • Kim, Sang-Beom;Lee, Gun-Woo;Kim, Hye-Young;Shim, Mi-Ja;Rho, Hyun-Su;Lee, Hyun-Sook;Lee, Min-Woong;Lee, U-Youn;Lee, Tae-Soo
    • The Korean Journal of Mycology
    • /
    • v.34 no.2
    • /
    • pp.98-104
    • /
    • 2006
  • Armillaria mellea, one of edible and medicinal mushroom belonging to Tricholomataceae of Basid-iomycota, has been known to have outstanding inhibitive effects on the sarcoma 180 and Erhrlich carcinoma of mice. Neutral salt soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr. NaCl, Fr, HW and Fr. MeOH, respectively) were extracted from the mushroom. In vitro cytotoxicity tests, crude polysaccharide were not cytotoxic against cancer cell lines such as NIH3T3 and Sarcoma 180 at the concentration of $1000{\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of $60{\sim}67.5%$ in mice inoculated with Sarcoma 180, respectively. Fr, NaCl improved the immunopotentiation activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.8{\sim}3.0$ folds, respectively. In case of Fr. NaCl, the numbers of peritoneal exudate cells and circulating leukocytes were increased by 10 and 2 folds, respectively.

Modulatory Effect of Four Azulene Derivatives from the Fruiting Bodies of Lactarius hatsudake on Interferon-$\gamma$ Production (젖버섯아재비 자실체로부터 분리한 Azulene계 화합물이 Interferon-$\gamma$ 생성에 미치는 영향)

  • Xu, Guang Hua;Kim, Jae-Wha;Li, Gao;Yoo, Ick-Dong
    • Journal of the Society of Cosmetic Scientists of Korea
    • /
    • v.36 no.2
    • /
    • pp.151-156
    • /
    • 2010
  • Investigation of secondary bioactive metabolites from the fruiting bodies of Lactarius hatsudake led to the isolation of four azulene derivatives by means of repeated column chromatography and preparative HPLC, and they were identified as 1-formyl-4-methyl-7-isopropyl azulene (1), lactaroviolin (2), 4-methyl-7-isopropyl-azulene-1-carboxylic acid (3), and 1-formyl-4-methyl-7-(1-hydroxy-1-methylethyl) azulene (4) by their physico-chemical properties and spectroscopic analysis. The isolated compounds were evaluated for the effects on modulation of cytokines in natural killer cell line (NK92 cells). Compounds 1 and 4 strongly inhibited IFN-$\gamma$ production in a dose-dependent manner, corresponding to 101.3 % and 92.7 % inhibition at 400 ${\mu}M$, and 11.9 % and 24.1 % at 100 ${\mu}M$, respectively, whereas compounds 2 and 3 showed weak inhibitory effect on INF-$\gamma$ production, corresponding to 45.9 % and 18.0 % inhibition at 400 ${\mu}M$.

Antioxidant activities of solvent extracts from different Glehnia Radix parts and their inhibitory effect against nitric oxide production in Raw 264.7 cell (해방풍 부위별 용매추출물의 항산화 활성 및 nitric oxide 생성 억제)

  • Gu, Yul-Ri;Kim, Sun-Won;Son, Yong-Won;Hong, Joo-Heon
    • Food Science and Preservation
    • /
    • v.24 no.1
    • /
    • pp.116-124
    • /
    • 2017
  • In this study, we compared the antioxidant and immuno-modulatory effects of water (HR, HL, HS), 70% ethanol (ER, EL, ES), and 70% methanol (MR, ML, MS) extracts of different parts (root, leaf, and seed) from Glehnia Radix. Yields were 17.40-30.17% for water extract, 11.47-28.67% for 70% ethanol extract, and 10.73-30.57% for 70% methanol extract, respectively. The total polyphenol and flavonoid contents of EL were 10.79 g/100 g and 2.01 g/100 g, respectively. The DPPH and ABTS radical scavenging activities of EL at $1,000{\mu}g/mL$ were 84.70% and 57.64%, respectively. The superoxide radical scavenging and ferric-reducing antioxidant power of EL at $1,000{\mu}g/mL$ were 84.05% and $975.28{\mu}M$, respectively. Moreover, 70% ethanol and 70% methanol extracts of root from Glehnia Radix significantly inhibited production of NO in LPS-stimulated macrophage RAW 264.7 cells without cytotoxicity. These results suggest that 70% ethanol and 70% methanol extracts of Glehnia Radix leaf may be a useful functional food material in the food industry.

Comparison of Immuno-Modulatory Regulatory Activities of Rubus coreanus Miquel by Ultra High Pressure Extracts Process (초고압 공정에 의한 복분자의 면역조절효능 비교)

  • Kwon, Min-Chul;Kim, Cheol-Hee;Na, Chun-Soo;Kwak, Hyeong-Geun;Kim, Jin-Chul;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.15 no.6
    • /
    • pp.398-404
    • /
    • 2007
  • This study was performed to investigate the enhancement of anticancer activities and immuno modulatary activities from R. coreanus. by ultra high pressure extracts process. The cytotoxicity on human kidney cell (HEK293) was showed below 19.5% in adding 1.0 $mg/m{\ell}$ concentration. The anticancer activity was increased over 10% by high pressure processing in AGS and A549 cells. The immune cell growth using human immune B and T cells was improved by the high pressure extracts of Rubus coreanus in adding 1.0 $mg/m{\ell}$ concentration. The secretion of two kinds of cytokine, the IL-6 and $TNF-{\alpha}$ from human immune B and T cells were also enhanced in adding extracts by high pressure process of R. coreanus. The ultra high pressure extraction technique showed high efficiency in extracting of bioactive compound. The ultra high pressure technique could be used combined with other technique to improve the extracting rate and extracting efficiency.

Ultrastructural Study on Development of the Superior Cervical Ganglion of Human Fetuses (인태아 상경신경절 발육에 관한 전자현미경적 연구)

  • Kim, Dae-Young;Kim, Baik-Yoon;Yoon, Jae-Rhyong
    • Applied Microscopy
    • /
    • v.28 no.2
    • /
    • pp.139-158
    • /
    • 1998
  • The development of the superior cervical ganglion was studied by electron microscopic method in human fetuses ranging from 40 mm to 260 mm of crown-rump length (10 to 30 weeks of gestational age). At 40 mm fetus, the superior cervical ganglion was composed of clusters of undifferentiated cell, primitive neuroblast, primitive supporting cell, and unmyelinated fibers. At 70mm fetus, the neuroblasts and their processes were ensheated by the bodies or processes of satellite cells. The cytoplasm of the neuroblast contained rough endoplasmic reticulum, mitochondria, Golgi complex, Nissl bodies and dense-cored vesicles. As the neuroblasts grew and differentiated dense-cored vesicles moved away from perikaryal cytoplasm into developing processes. Synaptic contacts between the cholinergic axon and dendrites of postganglionic neuron and a few axosomatic synapses were first observed at 70 mm fetus. At 90 mm fetus the superior cervical ganglion consisted of neuroblasts, satellite cells, granule-containing cells, and unmyelinated nerve fibers. The ganglion cells increased somewhat in numbers and size by 150 mm fetus. Further differentiation resulted in the formation of young ganglion cells, whose cytoplasm was densely filled with cell organelles. During next prenatal stage up to 260 mm fetus, the cytoplasm of the ganglion cells contained except for large pigment granules, all intracytoplasmic structures which were also found in mature superior cervical ganglion. A great number of synaptic contact zones between the cholinergic preganglionic axon and the dendrites of the postganglionic neuron were observed and a few axosomatic synapses were also observed. Two morphological types of the granule-containing cells in the superior cervical ganglion were first identified at 90 mm fetus. Type I granule-containing cell occurred in solitary, whereas type II tended to appeared in clusters near the blood capillaries. Synaptic contacts were first found on the solitary granule-containing cell at 150 mm fetus. Synaptic contacts between the soma of type I granule-containing cells and preganglionic axon termials were observed. In addition, synaptic junctions between the processes of the granule- containing cells and dendrites of postganglionic neuron were also observed from 150 mm fetus onward. In conclusion, superior cervical ganglion cells and granule-containing cells arise from a common undifferentiated cell precursor of neural crest . The granule-containg cells exhibit a local modulatory feedback system in the superior cervical ganglion and nay serve as interneurons between the preganglionic and postganglionic cells.

  • PDF

DAMGO, a ${\mu}-Opioid$ Agonist and Cholecystokinin-Octapeptide Have Dual Modulatory Effects on Capsaicin-Activated Current in Rat Dorsal Root Ganglion Neurons

  • Eun, Su-Yong;Kim, Ji-Mok;Lee, Ji-Hye;Jung, Sung-Jun;Park, Joo-Min;Park, Yun-Kyung;Kim, Dong-Kwan;Kim, Sang-Jeong;Kwak, Ji-Yeon;Kim, Jun
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.5 no.1
    • /
    • pp.71-78
    • /
    • 2001
  • Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current $(I_{CAP})$ were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of $I_{CAP}$ by DAMGO $({\mu}-opioid\;agonist)$ and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of $I_{CAP}$ was significantly increased by DAMGO and completely reversed after washout, while $I_{CAP}$ was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on $I_{CAP}$. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of $I_H$ were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of $I_{CAP}$ (5/13). DAMGO also increased $I_{CAP}$ amplitude significantly in the same cells. The amplitude of $I_{CAP}$ was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease $I_{CAP}$ presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.

  • PDF