• Korean Journal of Fisheries and Aquatic Sciences
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• v.48 no.3
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• pp.346-353
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• 2015

Glucocorticoids (GCs) are steroid hormones regulated through responses to stress to maintain diverse metabolic and homeostatic functions. GCs act on the glucocorticoid receptor (GR), a member of the nuclear receptor family. This study identified and characterized the GR gene from the big-belly seahorse Hippocampus abdominalis designating it HaGR. The open reading frame of the HaGR cDNA was 2,346 bp in length, encoding a 782-amino-acid polypeptide with a theoretical isoelectric point of 6.26 and predicted molecular mass of 86.8 kDa. Nuclear receptors share a common structural organization, comprising an N-terminal transactivation domain, DNA-binding domain, and C-terminal ligand-binding domain. The tissue-specific mRNA expression profile of HaGR was analyzed in healthy seahorses using a qPCR technique. HaGR mRNA was expressed ubiquitously in all of the tissues examined, with the highest expression levels in kidney, intestine, stomach, and gill tissues. The mRNA expression in response to immune challenge with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C), Edwardsiella tarda, and Streptococcus iniae revealed that it is inducible in response to pathogen infection. These results suggest that HaGR is involved in the immune response of the big-belly seahorse.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.163-169
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• 2011

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by $x^2$-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

• Molecules and Cells
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• v.37 no.3
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• pp.257-263
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• 2014

A mammalian cell renovates itself by autophagy, a process through which cellular components are recycled to produce energy and maintain homeostasis. Recently, the abundance of gap junction proteins was shown to be regulated by autophagy during starvation conditions, suggesting that transmembrane proteins are also regulated by autophagy. Transient receptor potential vanilloid type 1 (TRPV1), an ion channel localized to the plasma membrane and endoplasmic reticulum (ER), is a sensory transducer that is activated by a wide variety of exogenous and endogenous physical and chemical stimuli. Intriguingly, the abundance of cellular TRPV1 can change dynamically under pathological conditions. However, the mechanisms by which the protein levels of TRPV1 are regulated have not yet been explored. Therefore, we investigated the mechanisms of TRPV1 recycling using HeLa cells constitutively expressing TRPV1. Endogenous TRPV1 was degraded in starvation conditions; this degradation was blocked by chloroquine (CLQ), 3MA, or downregulation of Atg7. Interestingly, a glucocorticoid (cortisol) was capable of inducing autophagy in HeLa cells. Cortisol increased cellular conversion of LC3-I to LC-3II, leading autophagy and resulting in TRPV1 degradation, which was similarly inhibited by treatment with CLQ, 3MA, or downregulation of Atg7. Furthermore, cortisol treatment induced the colocalization of GFP-LC3 with endogenous TRPV1. Cumulatively, these observations provide evidence that degradation of TRPV1 is mediated by autophagy, and that this pathway can be enhanced by cortisol.

• The Korean Journal of Nuclear Medicine
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• v.24 no.1
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• pp.108-118
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• 1990

It is well known that the glucocorticoid suppresses the osteoblast and the calcitonin suppresses the osteoclast. If the calcitonin prevents the osteoporosis with increased Tc-99m MDP uptake in the long-term use of glucocorticoid, then the calcitonin has some activating effect on the bone formation. The immobilization operation was done on the left hind-leg of 16 male Sprague-Dawley rats weighing about 300 g each. For 12 weeks after operation,8 rats were injected 0.5 mg/kg dexamethasone, and the other 8 rats were injected 0.5 mg/kg dexamethasone and $1\;\bar{u}/kg$ eel calcitonin. The bone mineral content was measured by the single photon absorptiometry and the Tc-99m MDP uptake was used as an index of the osteoblastic activity. 1) The Tc-99m MDP uptakes in the dexamethasone treated group were lower than those in the dexamethasone and calcitonin treated group, and there was no significant difference in Tc-99m MDP uptakes between the immobilized and normal femurs. 2) The bone mineral contents in the dexamethasone treated group were significantly lower than in the dexamethasone and calcitonin treated group, and the immobilized femurs had tower BMC than normal femurs. 3) The slope of regression between the BMC and Tc-99m MDP uptake was stiff in the dexamethasone treated group, and flat in the dexamethasone and calcitonin group, which shows discrepancy between the bone resorption and formation resulting prevention of net bone loss in the dexamethasone and calcitonin treated group. In conclusion, the calcitonin has some effect on the bone formation, and further studies with urinary hydroxyproline and cyclic AMP are expected.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.95-111
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• 2022

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.33.1-33.17
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• 2022

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.1
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• pp.91-100
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• 2004

Objectives：The effects of repeated maternal separation on the expression of glucocorticoid receptor (GR) and cyclooxygenase-2(COX-2) in the hippocampus of rat pups at preweanling stage were evaluated. Methods：The experimental, Repeated Maternal Separation group(N=4) was separated from the mother for four hours a day over a period of ten days beginning with postnatal day 4. The Control group(N=4), on the other hand, did not separated from the mother at all. GR and COX-2 expression in the hippocampus was examined by immunohistochemistry on postnatal day 14. Results：It was determined that the number of GR-immunopositive cells in the dentate gyrus of the hippocampus was significantly increased in the Repeated Maternal Separation group. The numbers of COX-2-immunopositive cells in the CA1 and CA3 were also significantly higher in the Repeated Maternal Separation group. Conclusion：These results suggest that maternal separation may be a significant developmental stress that induces GR and COX-2 expression in the hippocampus of developing pups.

• Journal of Life Science
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• v.24 no.12
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• pp.1356-1363
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• 2014

Ghrelin is a 28 amino acid orexigenic peptide hormone that is secreted predominantly by tX/A cells in the stomach, and it plays a major role in energy homeostasis. Activated ghrelin has an n-octanoyl group covalently linked to the hydroxyl group of the Ser3 residue, which is critical for its binding to the G-protein coupled growth hormone secretagogue receptor-1a (GHS-R1a). According to recent reports, both ghrelin and its receptor, GHS-R1a, are expressed by a variety of immune cells, including T- and B-lymphocytes, monocytes, and dendritic cells, and ghrelin stimulation of leukocytes provides a potent immunomodulatory signal controlling systemic and age-associated inflammation and thymic involution. Here, we report that ghrelin protected murine thymocytes from dexamethasone (DEX)-induced cell death both in vivo and in vitro. Subsequently, we explored the molecular mechanisms of the antiapoptotic effect of ghrelin. According to our experiments, ghrelin inhibited the expression of proapoptotic proteins via the regulation of glucocorticoid receptor (GR) phosphorylation. As a result, ghrelin inhibited the proapoptotic activation of proteins, such as Caspase-3, PARP, and Bim. These data suggest that ghrelin, through GHS-R, inhibits the pathway to apoptosis by regulation of the proapoptotic protein activation signal pathway. They provide evidence that blocking apoptosis is an essential function of ghrelin during the development of thymocytes.

• Proceedings of the Korean Society of Life Science Conference
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• 2002.09a
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• pp.89-89
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• 2002

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.159.2-159
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• 1996

No Abstract, See Full Text