• Animal cells and systems
• /
• v.1 no.1
• /
• pp.81-86
• /
• 1997

We studied the mechanism of arachidonic acid on the secretion of a neurotransmitter in rat pheochromocytoma PC12 cells. Arachidonic acid inhibited the 70 mM $K^+$-induced secretion of norepinephrine. Arachidonic acid also inhibited the 70 mM $K^+$-induced $Ca^{2+}$ mobilization which is due to the opening of the voltage-sensitive $Ca^{2+}$ channels (VSCC). Both the half maximal inhibitory concentration ($IC_{50}$) of the norepinephrine secretion and VSCC coincided at 30 uM. The major oxidized metabolites of arachidonic acid, prostaglandins did not mimic the inhibitory effect of arachidonic acid. Nordihydroguaiaretic acid (NDGA) and indomethacin which are inhibitors of lipoxygenase and cyclooxygenase, respectively, did not block the inhibitory effect of arachidonic acid. The results suggest that arachidonic acid serves as a signal itself, not in the form of metabolites. The pretreatment of various $K^+$ channel blockers such as 4-aminopyridine, tetraethylarnmonium, glipizide, or glibenclamide also did not show any effect on the inhibitory effect of arachidonic acid. Through these results we suggest that arachidonic acid regulates VSCC directly and affects the secretion of neurotransmitters.

• Journal of Ginseng Research
• /
• v.40 no.4
• /
• pp.400-408
• /
• 2016

Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. Methods: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. Results: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.1
• /
• pp.15-23
• /
• 2003

Cellular redox state is known to be perturbed during ischemia and that $Ca^{2+}$ and $K^2$ channels have been shown to have functional thiol groups. In this study, the properties of thiol redox modulation of the ATP-sensitive $K^2$ ($K_{ATP}$) channel were examined in rabbit ventricular myocytes. Rabbit ventricular myocytes were isolated using a Langendorff column for coronary perfusion and collagenase. Single-channel currents were measured in excised membrane patch configuration of patch-clamp technique. The thiol oxidizing agent 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB) inhibited the channel activity, and the inhibitory effect of DTNB was reversed by dithiothreitol (disulfide reducing agent; DTT). DTT itself did not have any effect on the channel activity. However, in the patches excised from the metabolically compromised cells, DTT increased the channel activity. DTT had no effect on the inhibitory action by ATP, showing that thiol oxidation was not involved in the blocking mechanism of ATP. There were no statistical difference in the single channel conductance for the oxidized and reduced states of the channel. Analysis of the open and closed time distributions showed that DTNB had no effect on open and closed time distributions shorter than 4 ms. On the other hand, DTNB decreased the life time of bursts and increased the interburst interval. N-ethylmaleimide (NEM), a substance that reacts with thiol groups of cystein residues in proteins, induced irreversible closure of the channel. The thiol oxidizing agents (DTNB, NEM) inhibited of the $K_{ATP}$ channel only, when added to the cytoplasmic side. The results suggested that metabolism-induced changes in the thiol redox can also modulate $K_{ATP}$ channel activity and that a modulatory site of thiol redox may be located on the cytoplasmic side of the $K_{ATP}$ channel in rabbit ventricular myocytes.

• Archives of Pharmacal Research
• /
• v.29 no.1
• /
• pp.34-39
• /
• 2006

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

• Archives of Pharmacal Research
• /
• v.29 no.4
• /
• pp.310-317
• /
• 2006

We investigated the effects of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent, on the human ether-a-go-go-related gene (HERG) $K^+$ channels expressed in Xenopus oocytes. TNBS neutralizes the positively charged amino-groups of peptide N-terminal and lysine residues. External application of TNBS at 10 mM for 5 min irreversibly shifted the curves for currents at the end of the pulse and tail currents of HERG to a more negative potential and decreased the maximal amplitude of the $I_{tail}$ curve $(I_{tail,max})$. TNBS had little effect on either the activated current-voltage relationship or the reversal potential of HERG current, indicating that TNBS did not change ion selectivity properties. TNBS shifted the time constant curves of both activation and deactivation of the HERG current to a more hyperpolarized potential; TNBS's effect was greater on channel opening than channel closing. External $H^+$ is known to inhibit HERG current by shifting $V_{1/2}$ to the right and decreasing $I_{tail,max}$. TNBS enhanced the blockade of external $H^+$ by exaggerating the effect of $H^+$ on $I_{tail,max}$, not on $V_{1/2}$. Our data provide evidence for the presence of essential amino-groups that are associated with the normal functioning of the HERG channel and evidence that these groups modify the blocking effect of external $H^+$ on the current.

• Archives of Pharmacal Research
• /
• v.26 no.9
• /
• pp.739-746
• /
• 2003

Ultraviolet B (UVB) is known to induce apoptosis in human melanocytes. Here we show the cytoprotective effect of sphingosine-1-phosphate (S1P) against UVB-induced apoptosis. We also show that UVB-induced apoptosis of melanocytes is mediated by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, and that S1P prevents apoptosis by inhibiting this apoptotic pathway. We further investigated three major mitogen-activated protein (MAP) kinases after UVB irradiation. UVB gradually activated c-Jun N-terminal kinase (JNK) and p38 MAP kinase, while extracellular signal-regulated protein kinase (ERK) was inactivated transiently. Blocking of the p38 MAP kinase pathway using SB203580 promoted cell survival and inhibited the activation of caspase-3 and PARP cleavage. These results suggest that p38 MAP kinase activation may play an important role in the UVB-induced apoptosis of human melanocytes. To explain this cytoprotective effect, we next examined whether S1P could inhibit UVB-induced JNK and p38 MAP kinase activation. However, S1P was not found to have any influence on UVB-induced JNK or p38 MAP kinase activation. In contrast, S1P clearly stimulated the phosphorylation of ERK, and the specific inhibition of the ERK pathway using PD98059 abolished the cytoprotective effect of S1P. Based on these results, we conclude that the activation of p38 MAP kinase plays an important role in UVB-induced apoptosis, and that S1P may show its cytoprotective effect through ERK activation in human melanocytes.

• Fire Science and Engineering
• /
• v.33 no.2
• /
• pp.20-29
• /
• 2019

In this paper, the effect of spontaneous combustion inhibitor on the surface of coal stockpile in coal yard was investigated by numerical analysis. First, the numerical analysis method of the present study was compared with the results of the previous study by analyzing the case where the spontaneous combustion inhibitor was not applied, and the effect of preventing spontaneous combustion by various areas and positions for spraying spontaneous combustion inhibitor was analyzed. As a result, the larger the application area of the spontaneous combustion inhibitor, the more the effect of preventing spontaneous combustion by blocking the oxygen inflow into the coal stockpile, and the greater the effect of the spontaneous combustion prevention when spraying spontaneous combustion inhibitor from the bottom of the coal stockpile. Spontaneous combustion inhibitor should be sprayed effectively, considering the economic aspects, such as manufacturing cost etc.

• Journal of Environmental Impact Assessment
• /
• v.32 no.3
• /
• pp.176-186
• /
• 2023

Urban Heat Island (UHI) is caused by an energy imbalance in urban areas, where building design and land cover contribute to its amplification. To mitigate UHI, increasing green space is one of the well known and the most effective approach. This study aims aimed to identify specific components of green spaces that lower temperatures and demonstrate the cooling effects based on their size and composition. Forests within green spaces have had a greater impact on temperature reduction due to shading and blocking solar radiation. Although lakes also contributed to temperature reduction, the effect to cooling intensity was not significant. The cooling distance does not depended on green space size or composition. The study emphasizes that initial temperature has a strongerinfluence on cooling intensity than green space size, highlighting the importance of vegetation type within green spaces to achieve a cooling effect. These findings provide valuable insights for urban planning and the design of green spaces to mitigate the effects of the urban heat island.

• Research in Plant Disease
• /
• v.19 no.2
• /
• pp.108-113
• /
• 2013

Wilt damage on tomato plants caused by Ralstonia solanacearum has been increased as the areas of tomato cultivation increased during the warm seasons. Also, the tomato rootstocks used to prevent the disease occurrence are not effective in the highly prevailing regions. Therefore, bacterial wilt resistant eggplant rootstock EG203, collected from AVRDC, was tested for its effect to deter the Ralstonia solanacearum wilt disease in the greenhouses at Buyeo Tomato Experiment Station from 2003 to 2005, and at Gumi, Kyungpook province from 2009-2011. Planting of eggplant rootstock EG203 should be done three weeks before the planting of tomato scions so that they can have similar stem diameter (2.5-3.0 mm) and can be easily grafted. Both insertion and inarching grafting showed 93-96% success rates. In the greenhouse tests at Buyeo Tomato Experiment Station from 2003 to 2005, eggplant rootstock EG203-grafted tomatoes showed the disease occurrence of 4.3%. On the other hand, non-grafted or other commercial rootstock-grafted tomatoes showed disease occurrence of 58.0% and 25.0-36.7%, respectively. In the greenhouse tests at Gumi, Kyungpook province in 2009, the disease occurrence on the EG203-grafted and non-grafted tomatoes was 2-5% and 20-80%, respectively. In 2010, at Gumi, Kyungpook province, when the wilt disease occurred slightly, the tomatoes grafted with tomato rootstocks B-blocking and Chung-gang, and eggplant rootstock EG203 showed similar disease severities, but EG203-grafted tomatoes formed lately cluster, resulting in the reduction of yield compared to tomato-grafted tomatoes. In 2011, at Gumi, Kyungpook province, when the wilt disease occurred severely, the tomato rootstocks 'B-blocking' and Chung-gang and eggplant rootstock EG203-grafted tomatoes showed disease occurrences of 60-85% and 0-1%, respectively. Therefore, it was concluded that tomato rootstocks 'B-blocking' and 'Chung-gang' are more useful in the areas contaminated with low levels of pathogen and eggplant rootstock EG203 is more useful in the areas contaminated with high levels of pathogen.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.1
• /
• pp.62-66
• /
• 2002

Hypertension is not only a well-established cardiovascular risk factor but also increase the risk of atherosclerosis. Most studies conducted to investigate the effectiveness of treatment for cardiovascular disease such as hypertension have focused primarily on conventional drug and physiotherapeutic treatments. BanhabackchulChunma-tang(半夏白朮天麻湯:BCT) is popular herbal medicine used in clinic for the treatment of various symptoms of drulatory disorders and weakness of digestive system, including anorexa and nausea with vertigo, severe headache, vomiting and so on. However, the mechanisms underlying its efficacy are unknown. This study investigated the effects of BCT as an alternative medication on the contraction induced by phenylephrine and KCI in rat thoratic aorta. BCT revealed siginificant relaxation on phenylephrine-induced arterial contraction, but revealed noncompetitive effect on concentration responses of phenylephrine-induced contraction. Treatment of N-L/sup ω/ -argine methyl ester(L-NAME) and methylene blue(MB)(10/sup -5/M) reduced the relaxation of BCT. BCT also increased in vitro NO production. It suggest that the relaxation effect of BBT is related with NO pathway, becausse the effect of L-NAME and MB are due to inhibition of NO synthesis from endothelial cells. These results indicate that BCT would be effective in hypertension treatment and its mechanism of relaxtion on arterial contraction is likely to be related with NO production, blocking of α-receptor and signal transduction after receptor activation.