• Animal cells and systems
• /
• 제1권1호
• /
• 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
• /
• 제40권4호
• /
• 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
• /
• 제7권1호
• /
• 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
• /
• 제29권1호
• /
• 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
• /
• 제29권4호
• /
• 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
• /
• 제26권9호
• /
• 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.

• 한국화재소방학회논문지
• /
• 제33권2호
• /
• pp.20-29
• /
• 2019

본 논문에서는 저탄장 석탄더미 표면부에 자연발화 차단제를 도포하였을 경우 자연발화 현상에 미치는 영향을 수치해석적인 방법을 통해 살펴보았다. 먼저 자연발화 차단제를 도포하지 않은 경우를 해석하여 선행연구 결과와 비교하여 본 연구의 수치해석방법을 검증한 후 다양한 자연발화 차단제 도포영역 및 위치에 따른 자연발화 방지효과를 분석하였다. 그 결과, 자연발화 차단제의 도포영역이 넓을수록 석탄더미 내부로의 산소유입이 차단되어 발화방지 효과가 컸으며, 자연발화 차단제를 석탄더미 바닥에서부터 도포하여야 발화방지 효과가 더욱 큰 것으로 나타났다. 자연발화 차단제의 제조비용 등의 경제적인 측면을 고려하여 효과적으로 도포하여야 한다.

• 환경영향평가
• /
• 제32권3호
• /
• pp.176-186
• /
• 2023

도시열섬(Urban Heat Island; UHI)은 도시가 인근 지역에 비해 뜨거운 현상을 의미하며 도시 내부의 건물의 구성, 토지피복의 종류 등이 변화하기 때문에 발생한다. 도시열섬을 완화하기 위한 방법으로 녹지공간의 조성인데, 녹지가 제공하는 냉각효과의 경우 녹지의 내부 구성 요소 및 녹지의 크기에 따라 변화한다. 본 연구는 다양한 토지피복으로 구성된 수원시를 대상으로 녹지의 크기와 녹지를 구성하는 요소들에 따른 냉각효과의 차이를 확인하고, 녹지의 인근 토지피복에 따라 녹지로부터 제공되는 냉각효과의 차이를 고찰하고자 한다. 연구 결과, 녹지의 초기 온도는 산림의 비율이 높을수록, 그리고 호수가 존재할수록 낮아졌다. 냉각효과 중 하나인 냉각강도는 숲의 비율이 높을수록 강해졌지만, 초기 온도가 더 큰 영향을 미쳤다. 다만 냉각 거리는 녹지의 크기나 구성에 따라 달라지지 않음을 확인했다. 본 연구의 결과는 도시의 계획 시 열섬을 완화하기 위한 녹지 설계 방안을 제시한 다는 점에 의의를 가진다.

• 식물병연구
• /
• 제19권2호
• /
• pp.108-113
• /
• 2013

Ralstonia solanacearum에 의한 시들음 피해는 고온기 재배가 증가함에 따라 피해가 증가하고 있다. 이에 재배적 방법으로 토마토대목을 이용하고 있으나 병이 다 발생하는 지역에서는 효과가 기대에 미치지 못한다. 이에 따라서 AVRDC에서 수집한 풋마름병 저항성 가지 대목인 EG203을 재료로 하여 풋마름병 다 발생포장인 부여 토마토시험장 비닐하우스에서 2003-2005년, 구미시 비닐하우스에서 2009-2011년까지 두 곳에서 각각 3년간 실시하였다. EG203(가지)는 광발아 종자로 파종 시 육묘 트레이에 직접 파종하여야 하며 EG-203(가지)의 파종 적기는 토마토 접수보다 3주전에 파종해야 접수와 비슷한 경경(2.5-3.0 mm)에 도달하여 접목하기에 알맞았다. 접목방법은 맞접과 삽접이 93-96%의 활착률을 보여 대목으로 사용가능한 것으로 확인되었다. 접목 후 포장에 정식한 후의 풋마름병 발생을 2003년부터 2005년까지 3년 동안의 평균은 EG203(가지) 접목 시 4.3%로 실생의 58.0%보다 매우 낮았으며 대목용 품종의 25.0-36.7%보다도 낮게 나타났다. 구미에서 2009년부터 2011년까지 3년간 대목 효과에 대하여 시험한 결과는 2009년 5농가에서 EG203과 실생묘를 비교한 결과 EG203에서는 풋마름병 발생률이 2-5%였으나 실생은 20-80%를 보였다. 2010년에는 토마토대목('B-blocking', '청강')과 가지대목(EG203)을 갖고 비교 한 결과 풋마름병 발생률의 차이는 보이지 않았으나 가지대목(EG203)에서 복화방 출현이 늦어 수확이 감소되는 경향을 보였다. 2011년 토마토대목('청강')과 가지대목(EG203)으로 3농가에서 시험한 결과 토마토대목('청강')에서 풋마름병 발생률은 60-85%, 가지대목(EG203)은 0-1%로 가지대목에서 병발생률이 매우 낮았다. 가지대목(EG203)을 이용할 경우 토마토대목과 비교 복화방이 늦게 발생하여 토마토 생산량이 줄었다. 따라서 병 발생이 낮은 곳에서는 토마토대목을 활용하여 접목을 하고 병이 다 발생하는 지역에서는 가지대목(EG203)을 활용하는 것이 재배에 유리하다고 판단되어진다.

• 동의생리병리학회지
• /
• 제16권1호
• /
• 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.