• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.173-184
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• 1998

The present study was undertaken to examine the influence of glucocorticoids on the secretory responses of catecholamines (CA) evoked by acetylcholine (ACh), DMPP, McN-A-343, excess K^+$ and Bay-K-8644 from the isolated perfused rat adrenal gland and to clarify the mechanism of its action. The perfusion of the synthetic glucocorticoid dexamethasone (10-100\;{\mu}M$) into an adrenal vein for 20 min produced a dose-dependent inhibition in CA secretion evoked by ACh (5.32 mM), excess K^+$ (a membrane-depolarizor 56 mM), DMPP (a selective nicotinic receptor agonist, 100\;{\mu}M$ for 2 min), McN-A-343 (a muscarinic receptor agonist, 100\;{\mu}M$ for 4 min), Bay-K-8644 (a calcium channel activator, 10\;{\mu}M$ for 4 min) and cyclopiazonic acid (a releaser of intracellular $Ca^{2+}$, 10\;{\mu}M$ for 4 min). Similarly, the preperfusion of hydrocortisone (30\;{\mu}M$) for 20 min also attenuated significantly the secretory responses of CA evoked by nicotinic and muscarinic receptor stimulation as well as membrane-depolarization, $Ca^{2+}$ channel activation and the release of intracellular $Ca^{2+}$. Furthermore, even in the presence of betamethasone (30{\mu}M$), CA secretion evoked by ACh, excess K^+$, DMPP and McN-A-343 was also markedly inhibited. Taken together, the present results suggest that glucocorticoids cause the marked inhibition of CA secretion evoked by both cholinergic nicotinic and muscarinic receptor stimulation from the isolated perfused rat adrenal gland, indicating strongly that this inhibitory effect may be mediated by inhibiting influx of extracellular calcium as well as the release of intracellular calcium in the rat adrenomedullary chromaffin cells.

• Biomedical Science Letters
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• v.19 no.1
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• pp.32-40
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• 2013

Pluripotent stem cells (PSCs) have enormous potential in the biomedical sciences because they can grow continuously and differentiate into any kind of cell in the body. However, for future application in regenerative medicine, it is still a challenge to control the differentiation of PSCs without using genetic materials. To control the differentiation of PSCs, small molecules might be the best substitute for genetic materials considering the following advantages: small size, which enables penetration of plasma membrane; easy-to-modify structure; and low chance of genetic recombination in treated cells. Herein, we introduce small molecules that induce the neuroectodermal differentiation of mouse embryonic stem cells (ESCs). The small molecules were identified via ESC-based consecutive screenings of small-molecule libraries composed of 324 natural compounds or 93 selected drugs. The natural compounds discovered in the first screening were used to select 93 structurally similar drugs out of 1,200 approved drugs. In the second screening, among the 93 compounds, we found 4 drugs that induced the neuroectodermal differentiation of ESCs. These drugs were progesteroneor corticoid-derivatives. Our results suggest that small molecules targeting the progesterone receptor or glucocorticoid receptor could be used as chemical tools to induce the differentiation of PSCs into a specific germ lineage.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.54 no.5
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• pp.676-684
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• 2021

Euryhaline teleost have extraordinary ability to deal with a wide range of salinity changes. To study the seawater adaptability of rainbow trout Oncorhynchus mykiss (body weight 638±54 g, length 38.6±2 cm) to salinity increase fish were transferred from freshwater to 7, 14, 21, 28 and 32 psu and checked for mortality over 5 days. No mortality was observed in 0-32 psu. In fish transferred to 0-32 psu, blood osmolality was maintained within physiological range. The changes of serum enzyme activities (aspartate transaminase, AST and alanine transaminase, ALT) showed no significant level during experimental period. To explore the underlying molecular physiology of gill and kidney responsible for body fluid regulation, we measured mRNA expression of five genes, Na⁺/K⁺/2Cl^- cotransporter1 (NKCC1), aquaporin3 (AQP3), cystic fibrosis transmembrane conductance regulator (CFTR), glucocorticoid receptor (GR) and growth hormone receptor (GHR) in response to salt stress. Based on our result, rainbow trout could tolerate gradual transfer up to 32 psu for 5 days without mortality under physiological stress. This study suggests to alleviate osmotic stress to fish, a gradually acclimation to increasing salinity is recommended.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.217-221
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• 2012

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.11
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• pp.1628-1633
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• 2001

A goat ${\beta}$-casein gene was cloned and sequenced. Our previous study had determined the nucleotide sequences of the 5' flanking region and the structural gene including all 9 exons. In the present study, investigations were done on the regulatory sequences in the 5' flanking region of the goat ${\beta}$-casein gene by aligning and comparing it with the same gene from other mammals. The results showed that -200/-1 bp of the 5' flanking sequences contained six conserved clusters, in which the sites of gene expression regulated by the transcription factor and hormone might exist. It showed that fourteen glucocorticoid receptor elements, two cAMP responsive elements, two SV40 virus enhancer core sequences, two OCT-1 binding elements and one CTF/NF-1 binding element were dispersed in the 5' flanking region of goat ${\beta}$-casein gene. Our findings are perhaps valuable for the elucidation of the molecular mechanisms that control the expression of the goat ${\beta}$-casein gene.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.1-8
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• 2023

The herbal medication Panax ginseng Meyer has widespread use in China, Korea, and other parts of the world. The main constituents of ginseng are ginsenosides, which include over 30 different triterpene saponins. It has been found that ginsenosides and their metabolites including Rg1, compound K, Rb1, Re, Rg3, and Rg5 exert anti-inflammatory activities by binding to the glucocorticoid receptor, modulating inflammation-related signaling, including NF-κB and MAPK signaling, and reducing levels of proinflammatory cytokines. Here, we review the recent literature on the molecular actions of ginsenosides in sepsis, suggesting ways in which they may be used to prevent and treat the disease.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.224-230
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• 1998

This study showed the anti-invasive activity of ginseng components, panaxadiol (PD) and panamatrlol (PT) on the highly metastatic HT1080 human flbrosarcoma cell line. PD and PT reduced tumor cell invasion through a reconstitute basement membrane in the transwell chamber. A significant down regulation of MMP-9 by PD and PT was detected by northern blot analysis. However, MMP-2 was constantly expressed. Quantitative gelatin based zymography confirmed a marked reduced expression of MMP-9 but not MMP-2 in the treatment of PD and PT. Since the chemical structures of PD and PT are very similar to that of dexamethasone, a synthetic glucocorticoid, it was investigated whether PD and PT act through GR. Western blot analysis and immunocytochemistry showed that PD and PT increased the GR fraction in the nucleus. These results suggest that ursolic acid may induce repression of MMP-9 by stimulating the nuclear translocation of GR and hence inhibiting the activity of AP-1 to TPA-responsible element of MMP-9 promoter region. In conclusion, we suggest that CR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT 1080 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.393-398
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• 2012

Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress $Fc{\varepsilon}RI$-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE ($Fc{\varepsilon}R$) I and increased the mRNA levels of the inhibitory Fc receptor for IgG $Fc{\gamma}RIIb$. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG ($Fc{\gamma}R$) I and $Fc{\gamma}RIII$. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced $Fc{\gamma}RI$ and $Fc{\gamma}RIII$ mRNA levels potently, while $Fc{\varepsilon}RI$ and $Fc{\gamma}RIIb$ were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only $Fc{\gamma}RIIb$ protein expression was significantly enhanced by Dex treatment, while $Fc{\gamma}RI$, $Fc{\gamma}RIII$ and $Fc{\varepsilon}RI$ expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor $Fc{\gamma}RIIb$.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.123-132
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• 2018

Ginseng has gained its popularity as an adaptogen since ancient days because of its triterpenoid saponins, known as ginsenosides. These triterpenoid saponins are unique and classified as protopanaxatriol and protopanaxadiol saponins based on their glycosylation patterns. They play many protective roles in humans and are under intense research as various groups continue to study their efficacy at the molecular level in various disorders. Ginsenosides Rb1 and Rg1 are the most abundant ginsenosides present in ginseng roots, and they confer the pharmacological properties of the plant, whereas ginsenoside Rg3 is abundantly present in Korean Red Ginseng preparation, which is highly known for its anticancer effects. These ginsenosides have a unique mode of action in modulating various signaling cascades and networks in different tissues. Their effect depends on the bioavailability and the physiological status of the cell. Mostly they amplify the response by stimulating phosphotidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway, caspase-3/caspase-9-mediated apoptotic pathway, adenosine monophosphate-activated protein kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells signaling. Furthermore, they trigger receptors such as estrogen receptor, glucocorticoid receptor, and N-methyl-$\text\tiny{D}$-aspartate receptor. This review critically evaluates the signaling pathways attenuated by ginsenosides Rb1, Rg1, and Rg3 in various tissues with emphasis on cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders.