• Title/Summary/Keyword: Signalling Effect

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Role of ${\alpha}$-tocopherol in cellular signaling: ${\alpha}$-tocopherol inhibits stress-induced mitogen-activated protein kinase activation

  • Hyun, Tae-Kyung;Kumar, Kundan;Rao, Kudupudi Prabhakara;Sinha, Alok Krishna;Roitsch, Thomas
    • Plant Biotechnology Reports
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    • v.5 no.1
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    • pp.19-25
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    • 2011
  • Tocopherols belong to the plant-derived poly phenolic compounds known for antioxidant functions in plants and animals. Activation of mitogen-activated protein kinases (MAPK) is a common reaction of plant cells in defense-related signal transduction pathways. We report a novel non-antioxidant function of ${\alpha}$-tocopherol in higher plants linking the physiological role of tocopherol with stress signalling pathways. Pre-incubation of a low concentration of $50{\mu}M$ ${\alpha}$-tocopherol negatively interferes with MAPK activation in elicitor-treated tobacco BY2 suspension culture cells and wounded tobacco leaves, whereas pre-incubated BY2 cells with ${\alpha}$-tocopherol phosphate did not show the inhibitory effect on stimuli-induced MAPK activation. The decreased MAPK activity was neither due to a direct inhibitory effect of ${\alpha}$-tocopherol nor due to the induction of an inhibitory or inactivating activity directly affecting MAPK activity. The data support that the target of ${\alpha}$-tocopherol negatively regulates an upstream component of the signaling pathways that leads to stress dependent MAPK activation.

Market Responses and Liquidity Effect to Stock Splits in Korea (우리나라에서 주식분할에 따른 시장반응과 유동성효과)

  • Hwang, Sun-Wung;Shin, Woo-Yong
    • The Korean Journal of Financial Management
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    • v.24 no.4
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    • pp.201-232
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    • 2007
  • In this study, we investigated public announcements of stock splits using the Korean Stock Market data from 2000 through 2007. The purposes of this study are to examine whether stock splits have the information contents in the Korean capital markets, and to investigate the possible cause of the market reactions. We measured the market reactions with abnormal returns, cumulative abnormal returns and cumulative average abnormal returns. For the purpose, two specific hypotheses were tested. One is 'Signalling Effects' where stock splits function as a signal through which managers transmit a favorable information for investors. The other is 'Liquidity Effects' where stock splits increase the trading convenience. We have th following results. Firstly, positive market effects were found when stock splits were announced. Secondly, there was difference in trading convenience between the high and the low split ratios. Finally, the long term performance through stock splits in the Korean capital markets was not significant.

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FMECA Procedure for Failure Analysis of Train High-Speed Circuit Breaker (전동차 고속차단기 고장 분석을 위한 FMECA 기법)

  • Kim, Sung-Ryeol;Moon, Yong-Sun;Choi, Kyu-Hyoung
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.5
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    • pp.3370-3377
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    • 2015
  • FMECA(Failure Mode, Effects and Criticality Analysis) techniques to make quantitative evaluation of failure effects severity and criticality have been applied to systematic failure analysis for reliability improvement of train which should provide regular service and secure high level of safety as a mass transportation system. These FMECA techniques do not fully reflect the inherent train operation and maintenance circumstances because they are based on the FMECA standards devised for other industries such as automobile industry and FMECA standard dedicated to train industry has not been established yet. This paper analyzes FMECA standards for various industries, and suggests a FMECA technique dedicated to train industry which makes failure effect analysis and criticality analysis step by step and makes criticality analysis placing emphasis on the severity of the failure effect. The proposed technique is applied to FMECA of high-speed current breaker which is a core safety device of train using field failure data for 15 years of train maintenance. The FMECA results show that breakage of arc chute has the highest risk with 3rd severity class and 5th criticality class among all the components of high-speed circuit breaker. Damage and poor contact of electronic valve, and cylinder breakage with 3rd severity class and 4th criticality class are followed by. These results can be applied to improvement of design and maintenance process for high-speed circuit breaker of train.

Inhibitory Effect of Caffeine on Carbachol-Induced Nonselective Cationic Current in Guinea-Pig Gastric Myocytes

  • Kim, Sung-Joon;Min, Kyung-Wan;Kim, Young-Chul;Lee, Sang-Jin;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.3
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    • pp.353-359
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    • 1998
  • In gastrointestinal smooth muscle, muscarinic stimulation by carbachol (CCh) activates nonselective cation channel current ($I_{CCh}$) which is facilitated by intracellular [$Ca^{2+}$] increase. Caffeine is widely used in experiments to mobilize $Ca^{2+}$ from intracellular stores. This study shows a strong inhibitory effect of caffeine on $I_{CCh}$ in guinea-pig gastric myocyte. In this study, the underlying mechanism of the inhibitory effect of caffeine was investigated. $I_{CCh}$ was completely suppressed by the addition of caffeine (10 mM) to the superfusing solution. Inhibition of $I_{CCh}$ by caffeine was not related to the intracellular cAMP accumulation which was expected from the phosphodiesterase-inhibiting effect of caffeine. The blockade of $InsP_3-induced$ $Ca^{2+}$ release by heparin had no significant effects on the activation of $I_{CCh}$. When the same cationic current had been induced by intracellular dialysis of $GTP[{\gamma}S]$ in order to bypass the muscarinic receptor, the inhibitory effect of caffeine was significantly attenuated. The results of this study indicate that both intracellular signalling pathways for $I_{CCh}$, proximal and distal to G-protein activation, are suppressed by caffeine. A major inhibition was observed at the proximal level.

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Real Earnings Management and Persistence of Firm Value: Evidence from India

  • POTHARLA, Srikanth;BHATTACHARJEE, Kaushik;SAMONTARAY, Durga Prasad
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.12
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    • pp.323-336
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    • 2021
  • The present study aims to examine the impact of real earnings management on the future value of the firm and its persistence. The study also tests suspect firm effects on the relationship between real earnings management and the future value of the firm. The sample of the present study consists of all listed non-financial firms from the year 2011 to 2018. Real earnings management has been measured in three alternative ways viz., abnormal operating cash flows, abnormal discretionary spending, and abnormal production cost. Tobin's Q is used as a measure of firm value. The interaction term of real earnings management and Tobin's Q is used to test firm value persistence. The results of the analysis disclose that out of three measures of real earnings management, abnormal reduction in discretionary spending only has a significant negative impact on the persistence of firm value. Moreover, the suspect firm analysis reveals that when the underlying motive of real earnings management is to meet zero earnings, both abnormal increases in operating cash flows and abnormal reduction in discretionary spending have a significant negative impact on firm value persistence.

Convergence Studies of NO Homeostasis in Cellular Signalling (세포의 신호전달 과정에서 NO 항상성에 관한 융복합 연구)

  • Oh, Hee-Kyun;Do, Eun-Young;Park, Hae-Ryoung
    • Journal of Digital Convergence
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    • v.13 no.12
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    • pp.461-467
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    • 2015
  • Saussurea lappa is known for a variety of physiological activities as a component but has not known to show the effect of the cellular signaling pathway. We investigated the anti-inflammatory effects by Saussurea lappa ethanol extract on the LPS(lipopolysaccharide) induced nitric oxide (NO) production by RAW 264.7 cell line. It shows the expressions of iNOS and COX-2 at the transcriptional level (RT-PCR). The Saussurea lappa ethanol extract showed transcriptional expression levels of pro-inflammatory cytokine TNF- and IL-$1{\beta}$ induced by LPS(lipolysaccharide) in RAW264.7 cell line. Saussurea lappa ethanol extract reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the RNA levels in a concentration-dependent manner. The finding that ethanol extract of Saussurea lappa has an influence on NO (nitric oxide) homeostasis in the study of the action mechanism on the macrophage-mediated inflammatory reaction was considered in terms of convergence. And it is to provide an important basis for the prevention and treatment of inflammatory diseases in the future.

Regulation of Insulin-Sensitive Cyclic Nucleotide Phosphodiesterase in Adipocytes of Streptozotocin-Induced Diabetic Rats (Streptozotocin으로 당뇨병을 유발시킨 흰쥐의 지방세포에서 일어나는 Insulin-Sensitive Phosphodiesterase의 조절에 관한 연구)

  • Park, Kyung-Sun;Lee, Myung-Soon;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.253-261
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    • 1993
  • Possible changes in the role of insulin-sensitive cyclic nucleotide phosphodiesterase(PDE) in mediating the antilipolytic action of insulin were investigated in adipocytes from streptozotocin-induced diabetic rats. Isolated adipocytes prepared from epididymal adipose tissue were incubated, with or without insulin, at $37^{\circ}C$ for 15 min following pretreatment with various drugs or toxins, and three (plasma membranes, microsomal membranes, and cytosol) fractions prepared by differential centrifugation were then assayed for cAMP phosphodiesterase activity. The PDE activities only in the crude microsomal (P2) fractions were activated by insulin both in diabetic and control rats. The basal PDE activities in P2 fractions of adipocytes from diabetic rats were higher than those from control rats, although the maximal effects observed at 2 nM of insulin, $100\;{\mu}M$ of isoproterenol or the combination of both were not significantly different from each other. The insulin-stimulated PDE activities in P2 fractions of adipocytes from diabetic rats were not changed by PIA, a $A_{1}$ adenosine receptor agonist, whereas they were decreased to the basal PDE activities in those from control rats. In addition, the adipocytes from diabetic rats showed an increased sensitivity to pertussis toxin compared to those from controls. There were no differences between diabetic and control rats in the sensitivity of adipocytes to cholera toxin. These data indicate that the impaired signalling through inhibitory receptors such as adenosine receptors in adipocytes from streptozotocin-induced diabetes relates to the loss or the decreased function of $G_i$ proteins, and leads to the increased activity of the insulin-dependent PDE at the basal states.

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Enhanced supply of methionine regulates protein synthesis in bovine mammary epithelial cells under hyperthermia condition

  • Zhou, Jia;Yue, Shuangming;Xue, Benchu;Wang, Zhisheng;Wang, Lizhi;Peng, Quanhui;Xue, Bai
    • Journal of Animal Science and Technology
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    • v.63 no.5
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    • pp.1126-1141
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    • 2021
  • Recent evidence has shown that methionine (Met) supplementation can improve milk protein synthesis under hyperthermia (which reduces milk production). To explore the mechanism by which milk protein synthesis is affected by Met supplementation under hyperthermia, mammary alveolar (MAC-T) cells were incubated at a hyperthermic temperature of 42℃ for 6 h in media with different concentrations of Met. While the control group (CON) contained a normal amino acid concentration profile (60 ㎍/mL of Met), the three treatment groups were supplemented with Met at concentrations of 10 ㎍/mL (MET70, 70 ㎍/mL of Met), 20 ㎍/mL (MET80, 80 ㎍/mL of Met), and 30 ㎍/mL (MET90,90 ㎍/mL of Met). Our results show that additional Met supplementation increases the mRNA and protein levels of BCL2 (B-cell lymphoma-2, an anti-apoptosis agent), and decreases the mRNA and protein levels of BAX (Bcl-2-associated X protein, a pro-apoptosis agent), especially at an additional supplementary concentration of 20 ㎍/mL (group Met80). Supplementation with higher concentrations of Met decreased the mRNA levels of Caspase-3 and Caspase-9, and increased protein levels of heat shock protein (HSP70). The total protein levels of the mechanistic target of rapamycin (mTOR) and the mTOR signalling pathway-related proteins, AKT, ribosomal protein S6 kinase B1 (RPS6KB1), and ribosomal protein S6 (RPS6), increased with increasing Met supplementation, and peaked at 80 ㎍/mL Met (group Met80). In addition, we also found that additional Met supplementation upregulated the gene expression of αS1-casein (CSN1S1), β-casein (CSN2), and the amino acid transporter genes SLC38A2, SLC38A3 which are known to be mTOR targets. Additional Met supplementation, however, had no effect on the gene expression of κ-casein (CSN3) and solute carrier family 34 member 2 (SLC34A2). Our results suggest that additional Met supplementation with 20 ㎍/mL may promote the synthesis of milk proteins in bovine mammary epithelial cells under hyperthermia by inhibiting apoptosis, activating the AKT-mTOR-RPS6KB1 signalling pathway, and regulating the entry of amino acids into these cells.

Relaxation Effect of Synthetic Ceramide Analogues in Cat Esophageal Smooth Muscle Cells

  • Lee, Doo-Won;Park, Sun-Young;Ryu, Jung-Su;Kim, Sung-Hyo;Im, Chae-Uk;Choi, Su-Hang;Lee, Se-Eun;Ko, Sung-Kwon;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.4
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    • pp.137-142
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    • 2008
  • Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. $C_2$-ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the $C_2$-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited $C_2$-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the $C_2$-ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit $C_2$-ceramide induced contraction via PKC and MAPK dependent pathway.

Effects of Thujae Orientalis Folium (TOF) on Gene Expression of Human melanoma cells (SK-MEL-2) (측백엽(側柏葉)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향)

  • Jung, Min-Young;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.81-108
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    • 2010
  • Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.