• Title/Summary/Keyword: Radical mechanism

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Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

  • Hahm, Eu-Teum;Seo, Jung-Woo;Hur, Jin-Young;Cho, Young-Wuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.127-132
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    • 2010
  • Reactive oxygen species (ROS), which include hydrogen peroxide ($H_2O_2$), the superoxide anion (${O_2}^-{\cdot}$), and the hydroxyl radical ($OH{\cdot}$), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of $H_2O_2$ on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM $H_2O_2$ gradually potentiated mIPSCs. This potentiating effect of $H_2O_2$ was blocked by the pretreatment with either 10,000-unit/mL catalase or $300-{\mu}M$ N-acetyl-cysteine. The potentiating effect of $H_2O_2$ was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N -(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.

Cisplatin-induced Alterations of $Na^+$-dependent Phosphate Uptake in Renal Epithelial Cells

  • Lee, Sung-Ju;Kwon, Chae-Hwa;Kim, Yong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.2
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    • pp.71-77
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    • 2007
  • Cisplatin treatment increases the excretion of inorganic phosphate in vivo. However, the mechanism by which cisplatin reduces phosphate uptake through renal proximal tubular cells has not yet been elucidated. We examined the effect of cisplatin on $Na^+$-dependent phosphate uptake in opossum kidney (OK) cells, an established proximal tubular cell line. Cells were exposed to cisplatin for an appropriate time period and phosphate uptake was measured using $[^{32}P]$-phosphate. Changes in the number of phosphate transporter in membranes were evaluated by kinetic analysis, $[^{14}C]$phosphonoformic acid binding, and Western blot analysis. Cisplatin inhibited phosphate uptake in a time- and dose-dependent manner, and also the $Na^+$-dependent uptake without altering $Na^+$-independent uptake. The cisplatin inhibition was not affected by the hydrogen peroxide scavenger catalase, but completely prevented by the hydroxyl radical scavenger dimethylthiourea. Antioxidants were ineffective in preventing the cisplatin-induced inhibition of phosphate uptake. Kinetic analysis indicated that cisplatin decreased Vmax of $Na^+$-dependent phosphate uptake without any change in the Km value. $Na^+$-dependent phosphonoformic acid binding was decreased by cisplatin treatment. Western blot analysis showed that cisplatin caused degradation of $Na^+$-dependent phosphate transporter protein. Taken together, these data suggest that cisplatin inhibits phosphate transport in renal proximal tubular cells through the reduction in the number of functional phosphate transport units. Such effects of cisplatin are mediated by production of hydroxyl radicals.

Inhibition of melanogenesis by sodium 2-mercaptoethanesulfonate

  • Kim, Jeong-Hwan;Oh, Chang-Taek;Kwon, Tae-Rin;Kim, Jong Hwan;Bak, Dong-Ho;Kim, Hyuk;Park, Won-Seok;Kim, Beom Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.2
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    • pp.149-156
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    • 2020
  • Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

Black soybean anthocyanins attenuate inflammatory responses by suppressing reactive oxygen species production and mitogen activated protein kinases signaling in lipopolysaccharide-stimulated macrophages

  • Kim, Jin Nam;Han, Sung Nim;Ha, Tae Joung;Kim, Hye-Kyeong
    • Nutrition Research and Practice
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    • v.11 no.5
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    • pp.357-364
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    • 2017
  • BACKGROUND/OBJECTIVES: Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to $100{\mu}g/mL$. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. RESULTS: Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$, and pro-inflammatory cytokines, including tumor necrosis factor ${\alpha}$ and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). CONCLUSION: These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses.

Flame Spread Mechanism of a Blended Fuel Droplet Array at Supercritical Pressure

  • Iwahashi, Takeshi;Kobayashi, Hideaki;Niioka, Takashi
    • Journal of the Korean Society of Combustion
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    • v.7 no.1
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    • pp.15-22
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    • 2002
  • Flame spread experiments of a fuel droplet array were performed using a microgravity environment. N-decane, 1-octadecene, and the blends (50% : 50% vol.) of these fuels were used and the experiments were conducted at pressures up to 5.0 MPa, which are over the critical pressure of these fuels. Observations of the flame spread phenomenon were conducted for OH radical emission images recorded using a high-speed video camera. The flame spread rates were calculated based on the time history of the spreading forehead of the OH emission images. The flame spread rate of the n-decane droplet-array decreased with pressure and had its minimum at a pressure around half of the critical pressure and then increased again with pressure. It had its maximum at a pressure over the critical pressure and then decreased gradually. The pressure dependence of flame spread rate of 1-octadecene were similar to those of n-decan, but the magnitude of the spread rate was much smaller than that of n-decane. The variation of the flame spread for the blended fuel was similar to that of n-decane in the pressure range from atmospheric pressure to near the critical pressure of the blended fuel. When the pressure increased further, it approached to that of 1-octadecene. Numerically estimated gas-liquid equilibrium states proved that almost all the fuel gas which evaporated from the droplet at ordinary pressure consisted of n-decane whereas near and over the critical pressure, the composition of the fuel gas was almost the same as that of the liquid phase, so that the effects of 1-octadecene on the flame spread rate was significant.

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TRIZ-based Improvement of Glass Thermal Deformation in OLED Deposition Process (트리즈 기반 OLED 증착 공정의 글래스 열 변형 개선)

  • Lee, Woo-Sung;Choi, Jin Young
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.40 no.1
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    • pp.114-123
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    • 2017
  • The global small and mid-sized display market is changing from thin film transistor-liquid crystal display to organic light emitting diode (OLED). Reflecting these market conditions, the domestic and overseas display panel industry is making great effort to innovate OLED technology and incease productivity. However, current OLED production technology has not been able to satisfy the quality requirement levels by customers, as the market demand for OLED is becoming more and more diversified. In addition, as OLED panel production technology levels to satisfy customers' requirement become higher, product quality problems are persistently generated in OLED deposition process. These problems not only decrease the production yield but also cause a second problem of deteriorating productivity. Based on these observations, in this study, we suggest TRIZ-based improvement of defects caused by glass pixel position deformation, which is one of quality deterioration problems in small and medium OLED deposition process. Specifically, we derive various factors affecting the glass pixel position shift by using cause and effect diagram and identify radical reasons by using XY-matrix. As a result, it is confirmed that glass heat distortion due to the high temperature of the OLED deposition process is the most influential factor in the glass pixel position shift. In order to solve the identified factors, we analyzed the cause and mechanism of glass thermal deformation. We suggest an efficient method to minimize glass thermal deformation by applying the improvement plan of facilities using contradiction matrix in TRIZ. We show that the suggested method can decrease the glass temperature change by about 23% through an experiment.

Antioxidant effects and its mechanism of Cheongsimyeonjatang in Sasang Constitutional Medicine (청심연자탕(淸心蓮子湯)의 항산화(抗酸化) 효과(效果)와 기전(機轉)에 관한 연구(硏究))

  • Han, Byeung-Sam;Bae, Young-Chun;Song, Seung-Yun;Park, Hye Sun;Lee, Jae-Heung;Kim, Kyung-Yo
    • Journal of Sasang Constitutional Medicine
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    • v.16 no.1
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    • pp.130-147
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    • 2004
  • To investigate the antioxidant capacity of traditional Korean herb medicines, water extracts from 42 species which has been used for the Taeum constitution of Sasang Medicine, were tested on their antioxidant activity using radical scavenging effects against ABTS. Some Of them showed strong antioxidant capacities at $50{\mu}g$ concentration. And, antioxidant capacities of 2 prescriptions extract of Sasang Medicine, Cheongsimyeonja-tang and Yeoldahanso-tang, in the different concentration ($10{\mu}g$, $50{\mu}g$, and $100{\mu}g$) were determined. At the same time, the antiperoxidation effects of these 2 prescriptions extract were determined. Lipid peroxidation in brain homogenates induced by NADPH and $ADF-Fe^{2+}$ was strongly inhibited by Cheongsimyeonja-tang in vitro. The above-mentioned 2 prescriptions are a potent antioxidant capacity and antiperoxidation activity, further investigation into the in vivo antioxidant therapeutic potential for treatment of human disorders in brain tissue.

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The Scavenging Effect on NO, DPPH and Inhibitory Effect on IL-4 in Radix Cynanchi Wilfordii Herbal-Acupunture Solution (백하수오약침액(白何首烏藥鍼液)의 NO, DPPH 소거(消去) 및 IL-4 억제효과(抑制效果))

  • Kim, Dong-hyun;Seo, Jung-chul;Lim, Sung-chul;Jung, Tae-young;Han, Sang-won
    • Journal of Acupuncture Research
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    • v.20 no.4
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    • pp.42-52
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    • 2003
  • Objective: For designing an optimal countermeasure against ageing and ageing related disease, it is necessary to understand the ageing mechanism and other reactive species. Free radicals are associated with the mechanisam of biological ageing and age-related diseases. This study was performed to identifiy the scavenging effect of Radix Cynanchi Wilfordii Herbal-Acupunture Solution(RCWHA) on Nitric Oxide(NO), 1, 1-diphenyl-2-picryl-hydrazyl(DPPH) and Interleukin-4(IL -4). Methods: The activity to scavenge DPPH radicals and NO was observed in vitro, We evaluated the antioxidant activity of RCWHA by using DPPH or NO free radical method. Also the inhibitory effect on IL-4 in RCWHA was observed in vitro, Results: The followings are the summary of the results; (1) There is a significant scavenging effect of RCWHA on NO in 0.1mg/ml and 10mg/ml group after 24hrs. (2) There is no significant scavenging effect of RCWHA on DPPH. (3) There is a significant scavenging effect of RCWHA on IL-4 in $10{\mu}g/m{\ell}$ and $100{\mu}g/m{\ell}$ group. Conclusions: These findings indicate that RCWHA can be used as antioxidant or antiimflamatory drug. But further study is needed about the effect of RCWHA.

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Structural, Electrochemical, DNA Binding and Cleavage Properties of Nickel(II) Complex [Ni(H2biim)2(H2O)2]2+ of 2,2'-Biimidazole

  • Jayamani, Arumugam;Thamilarasan, Vijayan;Ganesan, Venketasan;Sengottuvelan, Nallathambi
    • Bulletin of the Korean Chemical Society
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    • v.34 no.12
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    • pp.3695-3702
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    • 2013
  • A nickel(II) complex $[Ni(H_2biim)_2(H_2O)_2](ClO_4)_2{\cdot}H_2O$ (1) of biimidazole ligand has been synthesized and characterized (Where $H_2biim$ = 2,2'-biimidazole). The single crystal X-ray diffraction of the complex shows a dimeric structure with six coordinated psudo-octahedral geometry. The cyclic voltammograms of complex exhibited one quasireversible reduction wave ($E_{pc}=-0.61V$) and an irreversible oxidation wave ($E_{pa}=1.28V$) in DMF solution. The interaction of the complex with Calf-Thymus DNA (CT-DNA) has been investigated by absorption and fluorescence spectroscopy. The complex is an avid DNA binder with a binding constant value of $1.03{\times}10^5M^{-1}$. The results suggest that the nickel(II) complex bind to CT-DNA via intercalative mode and can quench the fluorescence intensity of EB bind to CT-DNA with $K_{app}$ value of $3.2{\times}10^5M^{-1}$. The complex also shown efficient oxidative cleavage of supercoiled pBR322 DNA in the presence of hydrogen peroxide as oxidizing agent. The DNA cleavage by complex in presence of quenchers; viz. DMSO, KI, $NaN_3$ and EDTA reveals that hydroxyl radical or singlet oxygen mechanism is involved. The complex showed invitro antimicrobial activity against four bacteria and two fungi. The antimicrobial activity was nearer to that of standard drugs and greater than that of the free ligand.

Scavenging Activity of Reactive Oxygen Species and Inhibitory Effect of Cytochrome P450 from Circium japonicum Extract (대계 추출물의 할성산소 소거능 및 Cytochrome P450 효소 저해효과)

  • Kim, Hyuck;Yi, Hyo-Seung;Park, Won-Hwan;Moon, Jin-Young
    • The Korea Journal of Herbology
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    • v.22 no.1
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    • pp.53-61
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    • 2007
  • Objectives: Our previous studies have clearly demonstrated that the scavenging activity of reactive oxygen species (ROS), protective effect of lipid peroxidation (LPO), and inhibition of cytochrome P450 isozymes (CYPs) from the Circium japonicum aqua-acupuncture solution (CJAS). But, Circium japonicum water extracted solution (CJWS) was weakly reported in cardiovascular diseases such as oxidative stress-mediated atherosclerosis or its value evaluated. Methods: CJWS was assessed to determine the mechanism of its scavenging activity of ROS and inhibitory effect of CYP 2E1. Results: CJWS exhibited a concentration-dependent scavenger of DPPH and superoxide anions radicals using different assay systems. In addition, CJWS showed dose-dependent free radical scavenging activity, including hydroxyl radicals, peroxynitrite, and nitric oxide. The CJWS was also found to be effective in protecting rat liver homogenate against LPO. Futhermore, the CJWS showed significant inhibition of CYP 2E1 induced by pyrazol in a rat liver microsome. Conclusion : ROS and CYPs may play a role in several diseases, such as cardiovascular disease and heart failure. Our study demonstrated that the CJWS has excellent scavenging activity of ROS. Hence, it is worthwhile to investigate the potential effectiveness of CJWS in preventing oxidative stress-mediated cardiovascular diseases.

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