• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.225-231
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• 1997

As it has been reported that the depolarization-induced norepinephrine (NE) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor and various lines of evidence indicate the involvement of adenylate cyclase system in $A_1-adenosine$ post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the $A_1-receptor-mediated$ control of NE release in this study. Slices from rat hippocampus were equilibrated with $[^3H]-NE$ and the release of the labelled products was evoked by electrical stimulation.(3 Hz, $5Vcm^{-1}$, 2 ms, rectangular pulses). The influence of various agents on the evoked tritium-outflow was investigated. $N^6-Cyclopentyladenosine$ (CPA), a specific $A_1-adenosine$ receptor agonist, in concentrations Tanging from 0.1 to $10{\mu}M$ decreased the $[^3H]-NE$ release in a dose-dependent mauler without any change of basal rate of release. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, $2{\mu}M$), a selective $A_1-receptor$ antagonist, inhibited the CPA effect. The responses to N-ethylmaleimide $(3&10{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the CPA effects were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.1 to $30{\mu}M$ increased the evoked and basal rate of NE release in a dose-dependent manner and the CPA effects were inhibited by forskolin pretreatment. Rolipram $(1&10{\mu}M)$, a phosphodiesterase inhibitor, did not affect the evoked NE release but reduced the CPA effect. And 8-bromo-cAMP $(100&300{\mu}M)$, a membrane permeable cAMP analogue inhibited the CPA effect significantly. These results suggest that the $A_1-adenosine$ heteroreceptor plays an important role in NE-release via nucleotide-binding protein $G_i$ in the rat hippocampus and that the adenylate cyclase system might be participated in this process.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.25-33
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• 2016

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$)-dependent signaling affects the fate of cancer cells. Here we investigate the role of $Ca^{2+}$-activated $K^+$ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of dif-ferent cell lines; SNU-1076, OSC-19 and HN5. Treatment with $1{\mu}M$ ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of $Ca^{2+}$-activated $Cl^-$ channels (Ano-1) and $Ca^{2+}$-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward $K^+$ current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Con-sistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the $Ca^{2+}$ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.

• Applied Microscopy
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• v.33 no.4
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• pp.299-313
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• 2003

The aim of the present study was to assess the role of protein kinase C (PKC) in the development of cardiac injury following scald burn. Sprague-Dawley rats were induced a scald burn a 15% total body surface area. Phorbol 12-myristate 13-acetate (PMA, 2 mg/kg) and bisindolylmaleimide (BIS, 0.05 mg/kg) were immediately administered i.p. after burn injury. 5 h and 24 h later, heart was removed and examined biochemical assay, ultrastructural changes and stereological analysis. The activity of serum aspartate aminotransferase was significantly increased at 5h (p<0.01) and 5h+BIS (p<0.001) after burn compared with that of control. The activity of serum creatinine was significantly decreased in PMA-treated groups after burn compared with postburn 5 h. PMA caused a decrease in MPO activity and induced wavy fibers in cardiac myocytes at postburn 5 and 24h. BIS induced contraction band, separation of intercalated disk and abnormal mitochondria in cardiac myocytes at postburn 5 and 24h. In stereological analysis, treatment of rats with PMA increased volume density of myofibril and mitochondria compared with postburn 5 and 24h. Our data suggest that the activation of PKC in scald burned heart decreases inflammation and protects the myocardium.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.521-527
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• 2011

Recently, Korean ginseng, as immuno-activator, was actively investigated on its effect and mechanism. But purified fermented red ginseng (PFRG) has not been researched enough compared to red ginseng (RG, steamed and dried root of Panax ginseng C. A. Meyer, family Araliaceae) and fermented red ginseng (FRG, fermented red ginseng by Lactobacillus brevis 13094). In this study, we examined RG, FRG and PFRG to compare their anti-inflammatory effect by LPS. According to the result, RAW 264.7 cells survival rates did not largely change by RG and FRG. Only PFRG expressed weak toxicity at 10 ug/ml. The expression of iNOS and production of Nitric Oxide (NO) decreased depending on the concentration of RG, FRG and PFRG. And the expression of COX-2 also decreased. We tried western blotting for detecting that the expression of iNOS, COX-2 was caused by NF-${\kappa}B$. The result supported that the inhibition of NF-${\kappa}B$ by RG, FRG and PFRG suppressed the expression of iNOS, COX-2 and affected the production of TNF-${\alpha}$. While the anti-inflammatory effect was confirmed from all three types of red ginseng (RG, FRG, PFRG), the effect of PFRG was superior to others. Further research is required on other effects of PFRG.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.516-520
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• 2011

Osteoporosis is social problem around the world, because fracture of old age may lead to critical medical condition. Osteoclast is a main target for prevention and treatment of osteoporosis due to their responsibility for bone resorption. Saussureae Radix has been known that has gastro-protective, bronchodilatory effect and has a anti-biotic effect. Saussureae Radix has been widely used in Oriental medicine. However, the effect of extract of Saussureae Radix in osteoclast differentiation remains unknown. Thus, we examined the effect of Saussureae Radix in receptor activator of nuclear factor-${\kappa}$B ligand (RANKL)-induced osteoclast differentiation. From the results of our study, Here we found that Saussureae Radix significantly inhibited osteoclast differentiation induced by RANKL. Saussureae Radix suppressed the activation of NF${\kappa}$B in bone marrow macrophages (BMMs) treated with RANKL. Also, Saussureae Radix significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Saussureae Radix greatly inhibited the protein expression of c-fos and NFATc1. especially in the case of NFATc1 expression, a master transcription factor of the differentiation of osteoclasts is very important step for osteoclastogenesis. These results demonstrate that Saussureae Radix may be useful treatment option of bone-related disease such as osteoporosis and rheumatoid arthritis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.29-34
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• 2014

Bone homeostasis is maintained by balance between bone resorbing-osteoclasts and bone forming-osteoblasts. Excessive osteoclastic bone resorption plays a critical role in bone destruction in pathological bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. Many compounds derived from natural products have pharmacological applications and have therapeutic value for treating or preventing several bone diseases characterized by excessive bone resorption. To discover new compounds that can act as anti-resorptive agents, we screened for natural compounds that regulate osteclast differentiation, and found that water extract of Ziziphus Jujuba Mill (WEZJ) has inhibitory effects on osteoclast differentiation. In this study, WEZJ clearly inhibits the osteoclast differentiation in the presence of receptor activator of nuclear factor kB (RANKL), macrophage colony-stimulating factor (M-CSF) without cytoxicity by blocking activation of nuclear factor of activated T cells (NFAT)c1, and c-Fos. In signaling pathway, the phosphorylation of Akt, p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and the expression of osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphates (TRAP), Integrin av, Integrin b3, Cathepsin K are suppressed, too. These result suggest that WEZJ may have therapeutic value for treating or preventing several bone diseases characterized by excessive bone destruction.

• Toxicological Research
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• v.33 no.3
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• pp.225-231
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• 2017

National reference standards (NRSs) for biologics are established through potency estimation by a multi-center joint study of standard materials used in the approval process for national lot release and quality control of vaccines, blood products, and other biologics. In this study, a stability evaluation was conducted to determine whether the potency of NRSs for six blood products was being maintained at a consistent level in Korea. The present study conducted real-time stability tests via in-vivo/in-vitro bioassay on NRSs for blood coagulation factor VIII concentrate (2nd standard), antithrombin concentrate, prekallikrein activator, anti-hepatitis B immunoglobulin, blood coagulation factor IX concentrate, and anti-tetanus human immunoglobulin, as well as a trend analysis using cumulative annual results. The real-time stability test results showed that the mean potency of six NRSs was all within the control limit. In the trend analysis, the potency of NRS for blood coagulation factor VIII concentrate (2nd standard) showed a decreasing trend, while the potency of all other products had been stably maintained. The present study confirmed that the mean potency of NRSs for six blood products had been stably maintained in Korea. The findings of the present study establish a foundation that can ensure the quality of NRSs for biologics in Korea, and it is expected to make a major contribution to the supply of high-quality biologics.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Journal of Life Science
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• v.22 no.8
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• pp.1009-1017
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• 2012

The orf282 gene of Rhodobacter sphaeroides is located between the ccoNOQP operon encoding $cbb_3$ terminal oxidase and the fnrL gene encoding an anaerobic activator, FnrL. Its function remains unknown. In an attempt to reveal the function of the orf282 gene, we disrupted the gene by deleting a portion of the orf282 gene and constructed an orf282-knockout mutant. Two FnrL binding sites were found to be located upstream of orf282, and it was demonstrated that orf282 is positively regulated by FnrL. The orf282 gene is not involved in the regulation of spectral complex formation. The $cbb_3$ oxidase activity detected in the orf282 mutant was comparable to that in the wild-type sample, indicating that the orf282 gene is not involved in the regulation of the ccoNOQP operon and the biosynthesis of the cbb3 cytochrome c oxidase. The elevated promoter activity of the nifH and nifA genes, which are the structural genes of nitrogenase and its regulator, respectively, in the orf282 mutant, suggests that the orf282 gene product acts as a negative effector for nifH and nifA expression.

• Molecules and Cells
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• v.39 no.12
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• pp.855-861
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• 2016

Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-${\kappa}B$ ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro. Ginsenoside Re hampered osteoclast differentiation in a dose-dependent manner. In an in vivo zebrafish model, aqueous ginseng extract and ginsenoside Re had anti-osteoclastogenesis effects. These findings suggest that both aqueous ginseng extract and ginsenoside Re prevent bone resorption by inhibiting osteoclast differentiation. Ginsenoside Re could be important for promoting bone health.