• Title/Summary/Keyword: smooth

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The Src/PLC/PKC/MEK/ERK Signaling Pathway Is Involved in Aortic Smooth Muscle Cell Proliferation induced by Glycated LDL

  • Cho, Hyun-Mi;Choi, Sung Hee;Hwang, Ki-Chul;Oh, Sue-Young;Kim, Ho-Gyung;Yoon, Deok-Hyo;Choi, Myung-Ae;Lim, So Yeon;Song, Heesang;Jang, Yangsoo;Kim, Tae Woong
    • Molecules and Cells
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    • v.19 no.1
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    • pp.60-66
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    • 2005
  • Low density lipoproteins (LDL) play important roles in the pathogenesis of atherosclerosis. Diabetes is associated with accelerated atherosclerosis leading to cardiovascular disease in diabetic patients. Although LDL stimulates the proliferation of arterial smooth muscle cells (SMC), the mechanisms are not fully understood. We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. Addition of native and glycated LDL to rat aorta SMCs (RASMCs) stimulated ERK phosphorylation. ERK phosphorylation was not affected by exposure to the $Ca^{2+}$ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 ($5{\mu}M$) and inhibition of phospholipase C (PLC) with U73122/U73343 ($5{\mu}M$) all reduced ERK phosphorylation in response to glycated LDL. In addition, pretreatment of the RASMCs with a cell-permeable mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059, $5{\mu}M$) markedly decreased ERK phosphorylation in response to native and glycated LDL. These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular $Ca^{2+}$.

Berberine Inhibits the Production of Lysophosphatidylcholine-induced Reactive Oxygen Species and the ERK1/2 Pathway in Vascular Smooth Muscle Cells

  • Cho, Bong Jun;Im, Eun Kyoung;Kwon, Jun Hye;Lee, Kyung-Hye;Shin, Hye-Jin;Oh, Jaewon;Kang, Seok-Min;Chung, Ji Hyung;Jang, Yangsoo
    • Molecules and Cells
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    • v.20 no.3
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    • pp.429-434
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    • 2005
  • Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

WD Repeat Domain 1 Deficiency Inhibits Neointima Formation in Mice Carotid Artery by Modulation of Smooth Muscle Cell Migration and Proliferation

  • Hu, JiSheng;Pi, ShangJing;Xiong, MingRui;Liu, ZhongYing;Huang, Xia;An, Ran;Zhang, TongCun;Yuan, BaiYin
    • Molecules and Cells
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    • v.43 no.8
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    • pp.749-762
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    • 2020
  • The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.

Altered Calcium Current of the Vascular Smooth Muscle in Renal Hypertension

  • Nam, Sang-Chae;Jeong, Hye-Jeon;Kim, Won-Jae;Lee, Jong-Un
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.351-356
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    • 1999
  • The present study was aimed at investigating whether the calcium current in the vascular smooth muscle (VSM) cells is altered in renal hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in Sprague-Dawley rats. Rats without clipping the renal artery or implanting DOCA were used as control for 2K1C and DOCA-salt hypertension, respectively. Four weeks after clipping, systolic blood pressure was significantly higher in 2K1C rats than in control $(192{\pm}24\;and\;119{\pm}4$ mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure $(180{\pm}15$ mmHg, n=18) compared with control $(121{\pm}6$ mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured $5{\sim}10\;{\mu}m$ in width and $70{\sim}150\;{\mu}m$ in length were obtained. VSM cells could not be differentiated in size and shape between hypertensive and normotensive rats under light microscopy. High-threshold (L-type) calcium currents were recorded using whole-cell patch clamp technique. The amplitude of the current recorded from VSM cells was larger in 2K1C hypertension than in control. Neither the voltage-dependence of the calcium current nor the cell capacitance was significantly affected by 2K1C hypertension. By contrast, the amplitude of the calcium current was not altered in DOCA-salt hypertension. These results suggest that high-threshold calcium current of the VSM cells is altered in 2K1C hypertension, and that calcium channel may not be involved in calcium recruitment of VSM in DOCA-salt hypertension.

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Involvement of Spontaneously Formed Cyclic Nucleotides in Cat Gastric Muscle Relaxation

  • Sim, Sang-Soo;Baek, Hye-Jung;Rhie, Duck-Joo;Yoon, Shin-Hee;Hahn, Sang-June;Jo, Yang-Hyeok;Kim, Myung-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.275-282
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    • 1999
  • Muscle strips and muscle cells from cat stomach were used to investigate whether spontaneously formed cyclic nucleotides were involved in the inhibition of gastric smooth muscle contraction. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), increased the levels of both cyclic GMP (cGMP) and cyclic AMP (cAMP) in resting state cells, while decreasing acetylcholine-induced muscle contraction. Under the influence of IBMX, SQ22536, an adenylyl cyclase inhibitor and methylene blue, a guanylyl cyclase inhibitor completely blocked increases in cAMP and cGMP respectively, without any effect on contraction. However, the combination of SQ22536 and methylene blue completely blocked increases in both cAMP and cGMP levels and stimulated contractions markedly even in the presence of IBMX. Muscle contraction inhibitors such as isoprenaline, vasoactive intestinal polypeptide and sodium nitroprusside also appeared to increase cyclic nucleotide levels which decreased contraction. Which nucleotide increased the most was dependent on the agonist used. Therefore, irrespective of the cyclic nucleotide class, the spontaneous formation of cyclic nucleotides should be considered in evaluating the mechanism of gastric smooth muscle relaxation.

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Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

  • Han, Joo-Hui;Kim, Yohan;Jung, Sang-Hyuk;Lee, Jung-Jin;Park, Hyun-Soo;Song, Gyu-Yong;Nguyen, Manh Cuong;Kim, Young Ho;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.421-426
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    • 2015
  • The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

Effects of Antioxidants on the Gamma-Radiation Damage of the Cultured Vascular Smooth Mucle Cells of Rat Aorta

  • Lee, Jong-Doo;Choi, Hyoung-Chul;Kang, Young-Jin;Kim, Myung-Se;Lee, Kwang-Youn
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.5
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    • pp.189-195
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    • 2007
  • To study the protective effects of antioxidants on the radiation damages of the cells, vascular smooth muscle cells(VSMC) from thoracic aorta of Sprague-Dawley rats were cultured and irradiated with gamma-ray. Cell viability was measured by direct cell counting and MTT assay, and flow cytometry was performed to measure fractional distributions of the cells. Gamma-ray irradiation inhibited cell proliferations accompanied with decreased G1 phase and increased S- and G2/M phases, and the maximum effects were observed at 1500 or 2000 cGy. Submaximal concentrations of antioxidants, such as allopurinol, vitamin C, N-acetylcycteine(NAC), lipoic acid, dihydrolipoic acid and rebamipide tended to increase the cell viability suppressed by low dose of radiation(500 cGy), and enalapril and vitamin E increased it significantly. Allopurinol, vitamin E, NAC, lipoic acid, captopril and enalapril significantly increased G1 phase. Allopurinol and vitamin E tended to increase c-Myc expression, detected by Western blot, that was reduced by the radiation, and enalapril increased it significantly. The cell viability and c-Myc expression were highly correlated(r=0.97) with each other. These results suggest that antioxidants, especially enalapril and vitamin E, recover the viability of VSMC from gamma-radiation injury, through a mechanism which includes increase of c-Myc protein expression.

Smooth 핸드오프를 이용한 Mobile IP의 성능 분석

  • 차재정;김두용;최덕규
    • Proceedings of the Korea Society for Simulation Conference
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    • 2000.04a
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    • pp.23-24
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    • 2000
  • 최근 개인 이동 통신 단말기의 수요와 인터넷 사용자의 증가와 함께, 유선 통신 서비스에서부터 개인 휴대 통신 서비스에 이르기까지 다양한 통신 서비스가 제공되기 시작하면서 이러한 서비스가 결합된 mobile IP의 관심이 높아지고 있다. 기존의 IP에서는 노드가 계속해서 접속을 유지하기 위해서는 접속되는 위치가 반드시 고정적으로 지정되는 것이 필요하며 노드의 위치가 바뀌면 기존의 IP 주소는 사용할 수 없다. 그러나 mobile IP는 인터넷상의 임의의 다른 위치에 접속해 노드가 IP 주소를 바꾸지 않고 인터넷을 사용할 수 있도록 한다. 이동(mobile) 노드가 새로운 셀 지역으로 이동하면, 그 셀에 해당하는 외부(foreign) 에이전트로부터 임시 주소(care-of address)를 할당받아 홈 네트워크에 위치한 홈 에이전트에 등록하고, 홈 에이전트는 송신 노드가 이동노드로 전송한 패킷을 새롭게 등록된 임시 주소로 터널링을 통해 전달한다. 이러한 기본적인 mobile IP 방법은 모든 패킷이 홈 에이전트를 통해 이동 노드로 전송되므로 최적화된 라우팅 방법을 제공하지 못한다. 그러므로 이러한 mobile IP의 단점을 보완한 route optimization mobile IP가 제안되고 있다. Route optimization mobile IP는 이동 노드의 현재 위치와 관련된 정보를 갖는 바인딩을 저장하여 송신 노드가 패킷을 이동 노드의 홈 에이전트를 거치지 않고 이동 노드로 직접 전송하는 기능을 제공한다. 또한 이동 노드가 다른 셀 지역으로 핸드오프가 이루어질 경우, 핸드오프 발생전의 바인딩 정보를 이용하여 송신 노드가 전송한 패킷은 이전 셀 지역에 있는 에이전트가 새로운 셀 지역에 있는 이동 노드로 패킷을 재전송하여 전달하는 smooth 핸드오프 기능을 제공한다. 이전 셀 지역에 속한 외부 에이전트가 바인딩을 갱신하기 전에 송신 노드로부터 이동노드로 전달된 패킷이 있을 경우는 패킷을 저장하여 이후에 이동 노드의 위치 정보에 관한 바인딩 정보가 갱신되면 이러한 바인딩 정보에 따라 패킷을 재전송하는 버퍼기능도 제공한다. route optimization mobile IP는 기본적인 mobile IP에서의 복잡한 라우팅 문제를 해결하고, 핸드오프에서의 패킷 손실률을 최소화 한다.본 논문에서는 컴퓨터 시뮬레이션을 통해 smooth 핸드오프를 이용한 mobile IP의 성능을 분석한다. 일반적으로 데이터 트래픽 특성, 노드의 이동성, 바인딩 갱신시간, 버퍼관리 방법 등은 핸드오프 동안 mobile IP의 성능에 많은 영향을 미친다. 따라서 시뮬레이션 모델을 이용하여 다양한 트래픽 환경에서 위에 언급된 성능 파라미터들의 영향을 분석한다. 마지막으로 시뮬레이션 결과를 이용하여 mobile IP의 성능을 개선시키기 위한 방법을 제시한다.

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Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

  • Taqvi, Syed Intasar Hussain;Ghayur, Muhammad Nabeel;Gilani, Anwarul Hassan;Saify, Zafar Saeed;Aftab, Mohammad Tariq
    • Archives of Pharmacal Research
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    • v.29 no.1
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    • pp.34-39
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    • 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.

The Geometry of the Space of Symmetric Bilinear Forms on ℝ2 with Octagonal Norm

  • Kim, Sung Guen
    • Kyungpook Mathematical Journal
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    • v.56 no.3
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    • pp.781-791
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    • 2016
  • Let $d_*(1,w)^2 ={\mathbb{R}}^2$ with the octagonal norm of weight w. It is the two dimensional real predual of Lorentz sequence space. In this paper we classify the smooth points of the unit ball of the space of symmetric bilinear forms on $d_*(1,w)^2$. We also show that the unit sphere of the space of symmetric bilinear forms on $d_*(1,w)^2$ is the disjoint union of the sets of smooth points, extreme points and the set A as follows: $$S_{{\mathcal{L}}_s(^2d_*(1,w)^2)}=smB_{{\mathcal{L}}_s(^2d_*(1,w)^2)}{\bigcup}extB_{{\mathcal{L}}_s(^2d_*(1,w)^2)}{\bigcup}A$$, where the set A consists of $ax_1x_2+by_1y_2+c(x_1y_2+x_2y_1)$ with (a = b = 0, $c={\pm}{\frac{1}{1+w^2}}$), ($a{\neq}b$, $ab{\geq}0$, c = 0), (a = b, 0 < ac, 0 < ${\mid}c{\mid}$ < ${\mid}a{\mid}$), ($a{\neq}{\mid}c{\mid}$, a = -b, 0 < ac, 0 < ${\mid}c{\mid}$), ($a={\frac{1-w}{1+w}}$, b = 0, $c={\frac{1}{1+w}}$), ($a={\frac{1+w+w(w^2-3)c}{1+w^2}}$, $b={\frac{w-1+(1-3w^2)c}{w(1+w^2)}}$, ${\frac{1}{2+2w}}$ < c < ${\frac{1}{(1+w)^2(1-w)}}$, $c{\neq}{\frac{1}{1+2w-w^2}}$), ($a={\frac{1+w(1+w)c}{1+w}}$, $b={\frac{-1+(1+w)c}{w(1+w)}}$, 0 < c < $\frac{1}{2+2w}$) or ($a={\frac{1=w(1+w)c}{1+w}}$, $b={\frac{1-(1+w)c}{1+w}}$, $\frac{1}{1+w}$ < c < $\frac{1}{(1+w)^2(1-w)}$).