• Title/Summary/Keyword: Respiratory chain inhibitor

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Enzymatic Properties of the Membrane-bound NADH Oxidase System in the Aerobic Respiratory Chain of Bacillus cereus

  • Kim, Man-Suk;Kim, Young-Jae
    • BMB Reports
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    • v.37 no.6
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    • pp.753-756
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    • 2004
  • Membranes prepared from Bacillus cereus KCTC 3674, grown aerobically on a complex medium, oxidized NADH exclusively, whereas deamino-NADH was little oxidized. The respiratory chain-linked NADH oxidase exhibited an apparent $K_m$ value of approximately $65\;{\mu}m$ for NADH. The maximum activity of the NADH oxidase was obtained at about pH 8.5 in the presence of 0.1 M KCl (or NaCl). Respiratory chain inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) inhibited the activity of the NADH oxidase by about 90% at a concentration of $40\;{\mu}m$. Interestingly, rotenone and capsaicin inhibited the activity of the NADH oxidase by about 60% at a concentration of $40\;{\mu}m$ and the activity was also highly sensitive to $Ag^+$.

Fungicidal activity of synthetic piericidin analogs as inhibitors of NADH-ubiquinone oxidoreductase on the respiratory chain (호습쇄의 NADH-ubiquinone oxidoreductase 저해제인 합성 piericidin유사체드르이 살균활성)

  • Chung, Kun-Hoe;Cho, Kwang-Yun;Takahashi, Nobutaka;Yoshida, Shigeo
    • Applied Biological Chemistry
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    • v.33 no.3
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    • pp.264-267
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    • 1990
  • Representative synthetic piericidin-like compounds, such as hydroxypyridine and hydroxyquinoline derivatives, which showed high inhibition activity against NADH-ubiquinone oxidoreductase on the respiratory chain revealed good fungicide activity. Especially, hydrolrypyridine ones showed high activity against rice blast (Pyricularia oryzae) and barley powdery mildew (Erysiphe graminis).

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$Na^{+}$-dependent NADH:quinone Oxidoreductase in the Respiratory Chain of the Marine Bacterium Marinomonas vaga

  • Kim, Young-Jae;Park, Yong-Ha
    • Journal of Microbiology and Biotechnology
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    • v.6 no.6
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    • pp.391-396
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    • 1996
  • The Gram-negative marine bacterium Marinomonas vaga, which requires 0.5 M NaCl concentration for optimal growth, is slightly halophilic. The growth of M vaga was highly resistant to the proton conductor, carbonyl cyanide m-chlorophenylhydrazone (CCCP) under alkaline pH conditions (pH 8.5) but very sensitive to CCCP under acidic pH conditions (pH 6.5). These results suggest that the respiratory chain-linked NADH oxidase system of M. vaga may lead to generation of a $Na^{+}$ electrochemical gradient. In order to examine the existence of $Na^{+}$-stimulated NADH oxidase in M. vaga, membrane fractions were prepared by the osmotic lysis method. The membrane-bound NADH oxidase oxidized both NADH and deamino-NADH as substrates and required $Na^{+}$ for maximum activity. The maximum activity of NADH oxidase was obtained at about pH 8.5 in the presence of 0.2 M NaCl. The site of $Na^{+}$-dependent activation in the NADH oxidase system was at the NADH:quinone oxidoreductase segment. The NADH oxidase and NADH:quinone oxidoreductase were very sensitive to the respiratory chain inhibitor, 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) in the presence of 0.2 M NaCl but highly resistant to another respiratory inhibitor, rotenone. Based on these findings, we conclude that M. vaga possesses the $Na^{+}$-dependent NADH:quinone oxidoreductase that may function as an electrogenic $Na^{+}$ pump.

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A Novel All-trans Retinoid Acid Derivative N-(3-trifluoromethyl-phenyl)-Retinamide Inhibits Lung Adenocarcinoma A549 Cell Migration through Down-regulating Expression of Myosin Light Chain Kinase

  • Fan, Ting-Ting;Cheng, Ying;Wang, Yin-Feng;Gui, Shu-Yu;Chen, Fei-Hu;Zhou, Qing;Wang, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7687-7692
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    • 2014
  • Aim: To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)-retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. Materials and Methods: The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. Results: ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. Conclusions: ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down-regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.

Biological activity of quinoline derivatives as inhibitors of NADH-ubiquinone oxidoreductase in the respiratory chain (NADH-ubiquinone oxidoreductase 저해제인 quinoline 유도체들의 생리활성)

  • Chung, Kun-Hoe;Cho, Kwang-Yun;Takahashi, Nobutaka;Yoshida, Shigeo
    • Applied Biological Chemistry
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    • v.34 no.1
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    • pp.43-48
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    • 1991
  • New quinoline compounds were designed, synthesized, and examined with submitochondria. Most compounds showed high activity against NADH-ubiquinone oxidoreductase. Inhibition activity was mainly affected by the length of the lipophilic part, regardless of bulkiness or location of a phenyl group in the side chain. The $\beta-methyl$ group was demons)rated to be the optimal functionality on the nuclei of the quinoline derivatives so 4hat either deletion or insertion of a methylene on the group eliminated its activity.

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The Antifungal Test: An Efficient Screening Tool for the Discovery of Microbial Metabolites with Respiratory Inhibitory Activity

  • Han, Jae Woo;Kim, Bomin;Oh, Mira;Choi, Jaehyuk;Choi, Gyung Ja;Kim, Hun
    • Mycobiology
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    • v.48 no.4
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    • pp.326-329
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    • 2020
  • Valuable natural compounds produced by a variety of microorganisms can be used as lead molecules for development of new agrochemicals. Furthermore, high-throughput in vitro screening systems with specific modes of action can increase the probability of discovery of new fungicides. In the current study, a rapid assay tested with various microbes was developed to determine the degree of respiratory inhibition of Saccharomyces cerevisiae in two different liquid media, YG (containing a fermentable carbon source) and NFYG (containing a non-fermentable carbon source). Based on this system, we screened 100 fungal isolates that were classified into basidiomycetes, to find microbial secondary metabolites that act as respiratory inhibitors. Consequently, of the 100 fungal species tested, the culture broth of an IUM04881 isolate inhibited growth of S. cerevisiae in NFYG medium, but not in YG medium. The result is comparable to that from treatment with kresoxim-methyl used as a control, suggesting that the culture broth of IUM04881 isolate might contain active compounds showing the inhibition activity for respiratory chain. Based on the assay developed in this study and spectroscopic analysis, we isolated and identified an antifungal compound (-)-oudemansin A from culture broth of IUM04881 that is identified as Oudemansiella venosolamellata. This is the first report that (-)-oudemansin A is identified from O. venosolamellata in Korea. Taken together, the development of this assay will accelerate efforts to find and identify natural respiratory inhibitors from various microbes.

Regulation of Transient Receptor Potential Melastatin 7 (TRPM7) Currents by Mitochondria

  • Kim, Byung Joo;Jeon, Ju-Hong;Kim, Seon Jeong;So, Insuk;Kim, Ki Whan
    • Molecules and Cells
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    • v.23 no.3
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    • pp.363-369
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    • 2007
  • Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of $F_1/F_O$-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial $Ca^{2+}$ uniporter, and ruthenium red, an inhibitor of the mitochondrial $Ca^{2+}$ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the $F_1/F_O$-ATP synthase of mitochondria are important in regulating TRPM7 channels.

Isolation and Characterization of a New Hydrogen Sulfide-Oxidizing Bacterium Thiobacillus Sp. (황화수소 산화세균인 새로운 Thiobacillus sp.의 분리 및 특성)

  • Cha, Jin-Myeong;Lee, In-Hwa
    • Korean Journal of Microbiology
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    • v.32 no.4
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    • pp.252-257
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    • 1994
  • A new hydrogen sulfide-oxidation bacterium, Thiobacillus sp. was isolated from waste coal mine water around Hawsun in Chunnam province. The isolate was motile gram-negative rod shape, formed spore and grew up to be aerobically facultative chemolithotroph by using energy released from the oxidation of reduced inorganic sulfur compounds. It could assimilate various kinds of organic compounds and grew well upon thiosulfate-supplemented basal medium. To the lelvel of 32 mM in thiosulfate concentration, thiosulfate in itself was utilized as energy source for growth. However, from those of the higher concentration than 32 mM, thiosulfate functioned specifically as the substrate inhibitor rather than as the energy source. It was found that the optimum thiosulfate concentration for growth was 32 mM. The G+C content of the DNA was 65.0 mol%. The isolate had 16 : 1 + 17$_{cyc}$, 16 : 0 as their major non-hydroxylated cellular fatty acids, 3-OH 12 : 0 as a hydroxylated fatty acid and also contained unidentified $C_{18}$ branched fatty acid. The ubiquinone system in the respiratory chain was Q-9. Based on the physiological and biochemical characteristics, the isolate was assigned to a novel species of the genus Thiobacillus sp. iw.

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Function of NADPH Oxidases in Diabetic Nephropathy and Development of Nox Inhibitors

  • Lee, Sae Rom;An, Eun Jung;Kim, Jaesang;Bae, Yun Soo
    • Biomolecules & Therapeutics
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    • v.28 no.1
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    • pp.25-33
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    • 2020
  • Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H2O2), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.