• Title/Summary/Keyword: myosin phosphatase

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Korean Red Ginseng Improves Vascular Stiffness in Patients with Coronary Artery Disease

  • Chung, Ick-Mo;Lim, Joo-Weon;Pyun, Wook-Bum;Kim, Hye-Young
    • Journal of Ginseng Research
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    • v.34 no.3
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    • pp.212-218
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    • 2010
  • Korean red ginseng (KRG) has been shown to enhance endothelium-dependent vasorelaxation in experimental animals; however, little is known about its pharmacological effects on vascular stiffness in patients with coronary artery disease (CAD). This randomized, double-blind, placebo-controlled crossover trial was carried out to determine whether KRG has beneficial effects on arterial stiffness, cardiovascular risk factors such as plasma lipid profiles and blood pressure (BP), and Rho-associated kinase (ROCK) activity. Twenty patients (mean age, 62.5 years) with stable angina pectoris were given KRG (2.7 g/day) and a placebo alternatively for 10 weeks. Blood biochemical analysis and pulse wave velocity (PWV) recording were performed on day 0 and after the completion of each treatment. ROCK activity was assessed based on the level of phospho-$Thr^{853}$ in the myosin-binding subunit of myosin light chain phosphatase, determined by Western blot analysis of peripheral blood mononuclear cells. KRG significantly decreased the systolic BP, brachial ankle PWV, and heart femoral PWV in the patients (all p<0.05), but did not significantly alter the serum lipid profiles, including triglycerides and total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. The ROCK activity tended to decrease (p=0.068) following KRG treatment. The placebo did not significantly alter any of the variables. In conclusion, KRG decreased systolic BP and arterial stiffness, probably via the inhibition of ROCK activity, in patients with CAD, but had a neutral effect on serum lipid profiles. Our data suggest that KRG has a therapeutic effect on CAD.

Controversial Effect of Ethanol Irrespective of Kinases Inhibition on the Agonist-Dependant Vasoconstriction

  • Je, Hyun-Dong;Kim, Hyeong-Dong;Park, June-Hong
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.352-356
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    • 2012
  • The present study was undertaken to determine whether ethanol influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Ethanol significantly inhibited thromboxane $A_2$ mimetic-induced contraction with intact endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction irrespective of endothelium suggesting that the pathway such as Rho-kinase activation, $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, ethanol didn't decrease thromboxane $A_2$ mimetic-induced increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester-induced contraction in denuded muscles suggesting that thin filament regulation is less important on the ethanol-induced regulation in the muscle than endothelial NO synthesis. In conclusion, this study provides the evidence and possible related mechanism concerning the effect of ethanol on the agonist-dependent contraction in rat aortic rings with regard to endothelial function.

Regulatory Effect of Spray-Dried Lactiplantibacillus plantarum K79 on the Activation of Vasodilatory Factors and Inflammatory Responses

  • Ki Hwan Kim;Yongjin Hwang;Seok-Seong Kang
    • Food Science of Animal Resources
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    • v.44 no.1
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    • pp.216-224
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    • 2024
  • The reduction of nitric oxide (NO) bioavailability in the endothelium induces endothelial dysfunction, contributing to the development of hypertension. Although Lactobacillus consumption decreases blood pressure, intracellular signaling pathways related to hypertension have not been well elucidated. Thus, this study examined the effect of spray-dried Lactiplantibacillus plantarum K79 (LpK79) on NO production, intracellular signaling pathways, and inflammatory responses related to vascular function and hypertension. NO production was assessed in human umbilical vein endothelial cells (HUVECs) treated with LpK79. Endothelial NO synthase (eNOS) and intracellular signaling molecules were determined using Western blot analysis. LpK79 dose-dependently increased NO production and activated eNOS via the phosphoinositide 3-kinase/Akt signaling pathway HUVECs. Moreover, LpK79 mitigated the activation of crucial factors pivotal for vascular contraction in smooth muscle cells, such as phospholipase Cγ, myosin phosphatase target subunit 1, and Rho-associated kinase 2. When HUVECs were treated with LpL79 in the presence of Escherichia coli lipopolysaccharide (LPS), LpK79 effectively suppressed mRNA and protein expression of pro-inflammatory mediators induced by E. coli LPS. These results suggest that LpK79 provided a beneficial effect on the regulation of vascular endothelial function.

Endothelium Independent Effect of Pelargonidin on Vasoconstriction in Rat Aorta

  • Min, Young Sil;Yoon, Hyuk-Jun;Je, Hyun Dong;Lee, Jong Hyuk;Yoo, Seong Su;Shim, Hyun Sub;Lee, Hak Yeong;La, Hyen-Oh;Sohn, Uy Dong
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.374-379
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    • 2018
  • In this study, we investigated the effects of pelargonidin, an anthocyanidin found in many fruits and vegetables, on endothelium-independent vascular contractility to determine the underlying mechanism of relaxation. Isometric contractions of denuded aortic muscles from male rats were recorded, and the data were combined with those obtained in western blot analysis. Pelargonidin significantly inhibited fluoride-, thromboxane A2-, and phorbol ester-induced vascular contractions, regardless of the presence or absence of endothelium, suggesting a direct effect of the compound on vascular smooth muscles via a different pathway. Pelargonidin significantly inhibited the fluoride-dependent increase in the level of myosin phosphatase target subunit 1 (MYPT1) phosphorylation at Thr-855 and the phorbol 12,13-dibutyrate-dependent increase in the level of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at Thr202/Tyr204, suggesting the inhibition of Rho-kinase and mitogen-activated protein kinase kinase (MEK) activities and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxation effect of pelargonidin on agonist-dependent vascular contractions includes inhibition of Rho-kinase and MEK activities, independent of the endothelial function.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

  • Cho, Hyunhoo;Ok, Seong Ho;Kwon, Seong Chun;Lee, Soo Hee;Baik, Jiseok;Kang, Sebin;Oh, Jiah;Sohn, Ju-Tae
    • The Korean Journal of Pain
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    • v.29 no.4
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    • pp.229-238
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    • 2016
  • Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

Comparison of Gene Expression Levels of Porcine Satellite Cells from Postnatal Muscle Tissue during Differentiation

  • Jeong, Jin Young;Kim, Jang Mi;Rajesh, Ramanna Valmiki;Suresh, Sekar;Jang, Gul Won;Lee, Kyung-Tai;Kim, Tae Hun;Park, Mina;Jeong, Hak Jae;Kim, Kyung Woon;Cho, Yong Min;Lee, Hyun-Jeong
    • Reproductive and Developmental Biology
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    • v.37 no.4
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    • pp.219-224
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    • 2013
  • Muscular satellite cell (SC), which is stem cell of postnatal pig, is an important for study of differentiation into adipogenesis, myogenesis, and osteoblastogenesis. In this study, we isolated and examined from pig muscle tissue to determine capacity in proliferate, differentiate, and expression of various genes. Porcine satellite cells (PSC) were isolated from semimembranosus (SM) muscles of 90~100 days old pigs according to standard conditions. The cell proliferation increased in multi-potent cell by Masson's, oil red O, and Alizarin red staining respectively. We performed the expression levels of differentiation related genes using real-time PCR. We found that the differentiation into adipocyte increased expression levels of both fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) genes (p<0.01). Myocyte increased the expression levels of the myosin heavy chain (MHC), myogenic factor 5 (Myf5), myogenic regulatory factor (MyoD), and Myogenic factor 4 (myogenin) (p<0.01). Osteoblast increased the expression levels of alkaline phosphatase (ALP) (p<0.01). Finally, porcine satellite cells were induced to differentiate towards adipogenic, myogenic, and osteoblastogenic lineages. Our results suggest that muscle satellite cell in porcine may influence cell fate. Understanding the progression of PSC may lead to improved strategies for augmenting meat quality.