• Title/Summary/Keyword: CPI-17

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The Effect of Galangin on the Regulation of Vascular Contractility via the Holoenzyme Reactivation Suppressing ROCK/CPI-17 rather than PKC/CPI-17

  • Yoon, Hyuk-Jun;Jung, Won Pill;Min, Young Sil;Jin, Fanxue;Bang, Joon Seok;Sohn, Uy Dong;Je, Hyun Dong
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.145-150
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    • 2022
  • In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway. Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoride-dependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation

  • Hyuk-Jun Yoon;Heui Woong Moon;Young Sil Min;Fanxue Jin;Joon Seok Bang;Uy Dong Sohn;Hyun Dong Je
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.361-367
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    • 2024
  • In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

The Effect of Luteolin on the Modulation of Vascular Contractility via ROCK and CPI-17 Inactivation

  • Hyuk-Jun, Yoon;Dae Hong, Kang;Fanxue, Jin;Joon Seok, Bang;Uy Dong, Sohn;Hyun Dong, Je
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.193-199
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    • 2023
  • In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited increase in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.

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.

High fat diet confers vascular hyper-contractility against angiotensin II through upregulation of MLCK and CPI-17

  • Kim, Jee In
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.99-106
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    • 2017
  • Obesity is a critical risk factor for the hypertension. Although angiotensin II (Ang II) in obese individuals is known to be upregulated in obesity-induced hypertension, direct evidence that explains the underlying mechanism for increased vascular tone and consequent increase in blood pressure (BP) is largely unknown. The purpose of this study is to investigate the novel mechanism underlying Ang II-induced hyper-contractility and hypertension in obese rats. Eight-week old male Sprague-Dawley rats were fed with 60% fat diet or normal diet for 4 months. Body weight, plasma lipid profile, plasma Ang II level, BP, Ang II-induced vascular contraction, and expression of regulatory proteins modulating vascular contraction with/without Ang II stimulation were measured. As a result, high fat diet (HFD) accelerated age-dependent body weight gaining along with increased plasma Ang II concentration. It also increased BP and Ang II-induced aortic contraction. Basal expression of p-CPI-17 and myosin light chain (MLC) kinase was increased by HFD along with increased phosphorylation of MLC. Ang II-induced phosphorylation of CPI-17 and MLC were also higher in HFD group than control group. In conclusion HFD-induced hypertension is through at least in part by increased vascular contractility via increased expression and activation of contractile proteins and subsequent MLC phosphorylation induced by increased Ang II.

Flavone Attenuates Vascular Contractions by Inhibiting RhoA/Rho Kinase Pathway

  • Baek, In-Ji;Jeon, Su-Bun;Song, Min-Ji;Yang, Enyue;Sohn, Uy-Dong;Kim, In-Kyeom
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.3
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    • pp.201-207
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    • 2009
  • Our previous study demonstrated that flavone inhibits vascular contractions by decreasing the phosphorylation levelof the myosin phosphatase target subunit (MYPT1). In the present study, we hypothesized that flavone attenuates vascular contractions through the inhibition of the RhoA/Rho kinase pathway. Rat aortic rings were denuded of endothelium, mounted in organ baths, and contracted with either 30 nM U46619 (a thromboxane A2 analogue) or 8.0 mM NaF 30 min after pretreatment with either flavone (100 or 300 $({\mu}M$) or vehicle. We determined the phosphorylation level of the myosin light chain ($MLC_{20}$), the myosin phophatase targeting subunit 1 (MYPT1) and the protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light chain phophatase of 17-kDa (CPI17) by means of Western blot analysis. Flavone inhibited, not only vascular contractions induced by these contractors, but also the levels of $MLC_{20}$ phosphorylation. Furthermore, flavone inhibited the activation of RhoA which had been induced by either U46619 or NaF. Incubation with flavone attenuated U46619 or NaF-induced phosphorylation of $MYPT1^{Thr855}$ and $CPI17^{Thr38}$, the downstream effectors of Rho-kinase. In regards to the $Ca^{2+}$-free solution, flavone inhibited the phosphorylation of $MYPT1^{Thr855}$ and $CPI17^{Thr38}$, as well as vascular contractions induced by U 46619. These results indicate that flavone attenuates vascular contractions, at least in part, through the inhibition of the RhoA/Rho-kinase pathway.

The Association between Environmental Tobacco Smoke and Periodontal Health: Finding from Korean National Health and Nutrition Examination Survey 2008~2009 (간접흡연과 치주건강의 관련성: 2008~2009 국민건강영양조사 자료분석 결과)

  • Kim, Jin Kyoung;Baek, Hye-Jin;Lee, Young-Eun;Song, Keun-Bae;Choi, Youn-Hee
    • Journal of dental hygiene science
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    • v.14 no.2
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    • pp.123-131
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    • 2014
  • Environmental tobacco smoke (ETS) or second hand smoke or passive smoking has become a well-known risk factor for various health hazards in nonsmoking adults as well as active smokers. In Korea, there have been few studies concerning about the impact of ETS on periodontal health. Therefore, the aim of this study was to investigate the association between exposure to passive smoking and prevalence of periodontitis using Korea National Health and Nutrition Examination Survey (KNHANES) in 2008 and 2009. The Fourth KNHANES data was employed from 2008~2009. The final sample size was 4,669 adults aged over 18 years, who were never-smoker and had the information about ETS both at home and in the workplace, urine analysis and periodontal examination by Community Periodontal Index (CPI). Periodontitis was defined as CPI codes ${\geq}3$. Data were analyzed using PASW Statistics 18.0. The sociodemographic and behavioral factors were adjusted as confounders. Overall, 17.1% (male 16.4%, female 83.6%) of the participants were exposed to ETS. The mean concentration of cotinine in those exposed ETS was significantly higher than that in unexposed people ($46.92{\mu}g/ml$ versus $19.34{\mu}g/ml$, p<0.001). Participants exposed to ETS were more likely to have periodontitis than those unexposed after adjusting for potential confounding variables. ETS is associated with the prevalence of periodontitis in Korean adults. This may suggest that patients with periodontitis or periodontal surgery should be protected from smokers or smoking places.

The association between diabetes mellitus and community periodontal index: The 5th Korean National Health and Nutrition examination survey (당뇨와 지역사회치주지수의 관련성: 제5기 국민건강영양조사)

  • Kim, Young-Suk;Jeon, Ji-Hyun;Min, Hee-Hong
    • Journal of Korean society of Dental Hygiene
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    • v.14 no.6
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    • pp.805-812
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    • 2014
  • Objectives: The purpose of the study was to examine the association between diabetes mellitus and community periodontal index in Korean adults. Methods: The study populations were recruited by the Fifth Korea National Health and Nutrition Examination Survey. Study subjects were 10,411 who were examined oral examination, blood test, and aged over 19 years. Using multiple logistic regression analyses, the variables were adjusted for gender, age, household income, family history of diabetes, body mess index, smoking habit, and frequency of tooth brushing. Periodontal tissue examination of the subjects was performed and scored by Community periodontal index(CPI). Using probe, six teeth were examined for hemorrhage, plaque, and pocket depth and classified into $CPI_0$, $CPI_1$, $CPI_2$, $CPI_3$ and $CPI_4$. Healthy periodontal groups($CPI_{0-2}$) and periodontal disease groups($CPI_{3-4}$) were divided by the periodontal disease status. The definition of diabetes mellitus(DM) was decided by the diagnosis by the doctors and fasting blood sugar level. Those who were diagnosed as DM were included in DM group. The DM variables included normal blood sugar level, increased fasting blood sugar level, and DM blood sugar level. The DM variables were compared to periodontal disease blood sugar level and analyzed. Results: The periodontitis prevalence rate was 23.2%. Those who had diabetes mellitus accounted for 5.5% of the subjects. Those who had impaired fasting glucose accounted for 17.7% and 7.9% of subjects were diabetes mellitus by blood test. In the confirmed diabetes group by doctor, the periodontitis prevalence rate was significantly higher than the non-diabetic group. Diabetic group by blood test had the highest prevalence rate of periodontitis than those who had impaired fasting glucose group or normal group. After adjusting for gender, age, household income, family history of diabetes, body mass index, smoking habit, and frequency of tooth brushing, the risk of periodontitis in diagnosed diabetes mellitus was 1.57 times(95% CI; 1.27-1.94) higher than the normal group. In impaired fasting glucose group and diabetes mellitus group by blood test, the risk of periodontitis was 1.11 times(95% CI; 0.95-1.30) and 1.45 times(95% CI; 1.45-2.12) higher, respectively. Conclusions: There was a significant relationship between diabetes mellitus and periodontitis in Korean adults. These results suggest that diabetes mellitus is a risk factor for periodontitis.

Isolation and characterization of a cDNA encoding a mammalian cathepsin L-like cysteine proteinase from Acanthmoeba healui

  • Hong, Yeon-Chul;Hwang, Mi-Yul;Yun, Ho-Cheol;Yu, Hak-Sun;Kong, Hyun-Hee;Yong, Tai-Soon;Chung, Dong-Il
    • Parasites, Hosts and Diseases
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    • v.40 no.1
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    • pp.17-24
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    • 2002
  • We have cloned a cDNA encoding a cysteine proteinase of the Acanthamoeba healui OC-3A strain isolated from the brain of a granulomatous amoebic encephalitis patient. A DNA probe for an A. healui cDNA library screening was amplified by PCR using degenerate oligonucleotide primers designed on the basis of conserved amino acids franking the active sites of cysteine and asparagine residues that are conserved in the eukaryotic cysteine proteinases. Cysteine proteinase gene of A. healui (AhCPI) was composed of 330 amino acids with signal sequence, a proposed pro-domain and a predicted active site made up of the catalytic residues, $Cys^{25},{\;}His^{159},{\;}and{\;}Asn^{175}$. Deduced amino acid sequence analysis indicates that AhCPI belong to ERFNIN subfamily of C 1 peptidases. By Northern blot analysis. no direct correlation was observed between AhCPI mRNA expression and virulence of Acanthamoeba, but the gene was expressed at higher level in amoebae isolated from soil than amoeba from clinical samples. These findings raise the possibility that AhCPI protein may play a role in protein metabolism and digestion of phagocytosed bacteria or host tissue debris rather than in invasion of amoebae into host tissue.

Dynamic Spillover for the Economic Risk in Korea on Global Uncertainty

  • Jeon, Ji-Hong
    • Journal of Distribution Science
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    • v.17 no.1
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    • pp.11-19
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    • 2019
  • Purpose - We document the impact of economic policy uncertainty (EPU) in the US and China on the dynamic spillover effect of macroeconomics such as stock price, housing price in Korea. Research design, data, and methodology - We use the nine variables to analyze the effect which produces a result among the EPU indexes of the US and China on economic variables which is the consumer price index (CPI), housing purchase price composite index, housing lease price, the stock price index in banking industry, construction industry and distribution industry, and composite leading indicator from January 1995 to December 2016 with the Vector Error Correction Model. Result - The US EPU index has significantly a negative relation on the CPI, housing purchase price index, housing lease price index, the stock price index in banking industry, construction industry, and distribution industry in Korea. Conclusions - We find the dynamic effect of the EPU indexes in the US and China on the macroeconomics returns in Korea. This study has an empirical evidence that the economy market in Korea is influenced by the EPU index of the US rather than it of China. The higher EPU, the more risky the economy of in Korea.