• Title/Summary/Keyword: aldehyde dehydrogenase

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Identification of Differentially Expressed Genes by TCDD in Human Bronchial Cells: Toxicogenomic Markers for Dioxin Exposure

  • Park, Chung-Mu;Jin, Kyong-Suk;Lee, Yong-Woo
    • Biomedical Science Letters
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    • v.18 no.1
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    • pp.1-9
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    • 2012
  • Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

Comparison of Nelumbinis Semen Extract with Hypericum Perforatum and Fluoxetine in Animal Model of Depression (연자육의 항우울 효과 및 프로티옴 분석을 통한 기전 연구)

  • Lee, Jin-Woo;Hong, Moo-Chang;Shin, Min-Kyu;Bae, Hyun-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.830-843
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    • 2006
  • Clinical evidence suggests that Nelumbinis Semen extracts have antidepressive properties and may offer an interesting alternative for the treatment of mood disorders. It was the aim of the present study to compare the effects of Nelumbinis Semen extracts with those of fluoxetine and hypericum perforatum extract in the rat forced swimming test (FST) and chronic mild stress (CMS), a model of depression. In the FST, p.o. administration of Nelumbinis Semen extracts (1 mg) induced a statistically significant reduction of immobility. The active behaviors in that test did not reflect decreased general activity because Nelumbinis Semen extracts failed to alter the locomotor activity of rats, measured in the open field test. Moreover Nelumbinis Semen extracts was superior to fluoxetine and hypericum perforatum extract in the incidence of sexual side-effects. These effects of Nelumbinis Semen extracts on the rat behavior is to be ascribed to increased Cytochrome c oxidase polypeptide Vla-liver, Mitogen-activated protein kinase 1 , Adenylosuccinate synthetase, and Aldehyde dehydrogenase in rat hippocampus.

Effect of Ginsenosides on Bovine Liver Mitochondria Aldehyde Dehydrogenase Activity (인삼사포닌이 소의 간 미토콘드리아 ALDH 활성에 미치는 영향)

  • Kim, Sun-Jin;Lee, Hee-Bong;Joo, Chung-No
    • Journal of Ginseng Research
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    • v.18 no.1
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    • pp.10-16
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    • 1994
  • Effects of ginsenosides on the activities of bovine liver mitochondrial matrix ALDH and membrane bound ALDH were observed in vitro and it was found that both matrix and membrane bound ALDH were stimulated appreciably. The maximum activity for the matrix AkDH was found at the concentration of ginsenoside mixture being $10^{-7}$~$10^5$% and that for the membrane bound ALDH was at $10^{-6}$~$10^{-4}$%. It was also found that Km values of both ALDHS were lowered and their maximum velocity was increased. It was realized that the bovine liver mitochondrial matrix AkDH is Quite specific for the oxidation of low aliphatic aldehydes such as acetaldehyde and propionaldehyde. Therefore the increase of Vmax/Km value of the matrix ALDH in the presence of ginsenosides suggest that ginsenosides might stimulate the ALDH activity thereby resulting in the quick removal of harmful acetaldehyde from the liver to protect its toxicity.

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Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

  • Park, Seo-Ro;Joo, Hong-Gu
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.3
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    • pp.157-164
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    • 2022
  • Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

Synergistic anticancer activity of disulfiram/copper against mouse lymphoma cells (마우스 림프종세포에 대한 disulfiram/copper의 항암증진효과)

  • Jung, Haebeen;Joo, Hong-Gu
    • Korean Journal of Veterinary Research
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    • v.62 no.1
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    • pp.3.1-3.7
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    • 2022
  • Disulfiram (DSF) is a marketed drug to treat patients with alcohol dependence by inhibiting aldehyde dehydrogenase. Over the last few decades, DSF has been shown to have anticancer effects through different mechanisms. Moreover, this effect can be elevated when used with copper (Cu). Subsequent studies have been conducted on various cancers, but few on lymphoma. This study investigated the anticancer effects of DSF on lymphoma and how this effect changed when treated with Cu. DSF synergistically decreased the metabolic activity of EL4 lymphoma cells when combined with Cu. At 1 µM of DSF alone, the metabolic activity of EL4 cells decreased by 49% compared to the control, whereas it decreased by 87% with a DSF + CuCl2 treatment. Rhodamine 123 and 2',7'-dichlorofluorescein diacetate staining showed that DSF induced the reduction of the mitochondrial membrane potential and promoted the production of reactive oxygen species. In particular, the combined treatment of DSF + Cu induced cell death based on multiple assays, including annexin V-fluorescein isothiocyanate/propidium iodide staining. Overall, DSF has anticancer effects on lymphoma cells and exhibits synergistic effects when combined with Cu. This study provides some valuable information to broaden the use of DSF in clinics and basic research.

Isolation of Anticonvulsant Compounds from the Fruits of Schizandra chinensis$B_{AILI}$ (오미자(Schizandra chinensis $B_{AILI}$.) 열매로부터 항경련 활성물질의 분리)

  • Han, Jae-Taek;Ahn, Eun-Mi;Park, Jin-Kyu;Cho, Sung-Woo;Jeon, Seong-Gyu;Jang, Joong-Sik;Kim, Choong-Kwon;Choi, Soo-Young;Baek, Nam-In
    • Applied Biological Chemistry
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    • v.43 no.1
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    • pp.72-77
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    • 2000
  • The repeated silica gel colum chromatographies of EtOAc fraction, showing anticonvulsant activity, obtained from MeOH extracts of Schizandra chinensis B. fruits led to isolation of a sesquiterpenoid, four lignans and a sterol glycoside. Their chemical structures were determined to be chamigrenal, gomisin A, gomisin H, gomisin N. schizandrin and daucosterol. Among them, schizandrin and daucosterol inhibited GABA degrative enzymes, succinic semialdehyde dehydrogenase and succinic semialdehyde reductase, respectively. It is postulated that the schizandrin and daucosterol are able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on GABA degrative enzymes and act as anticonvulsant drugs.

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Bromate Formation by Ozonation Process and It′s Effect on Renal Toxicity in rat (오존처리에 의한 Bromate의 생성 및 흰쥐의 신장독성에 미치는 영향)

  • 정운용;이무강;최종원
    • Journal of Life Science
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    • v.12 no.4
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    • pp.442-451
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    • 2002
  • In oder to investigate the effects of pH and temperature on the formation of bromate ion, which is ozonation by-products of bromine containing natural water. At the same intial pH condition, the increase of pH shown similar trends even if the reaction variables such as temperature and reaction time of ozonation were changed. As pH and temperature were increasing, the bromate concentration was increased but bromine components (HOBr/OBr-) were decreased with increasing pH from 3 to 10. Lipid peroxide content in the kidney was increased by bromate which was ingestion with 0.4g/L for 24 weeks in drinking water. Renal cytosolic enzyme system (XO, AO) of bromate group were significantly increased in comparison with those of normal group. But microsomal enzyme system were not affected. BUN level and urinary ${\gamma}$-glutamyltransferase activity were significantly increased in comparison with those of the normal. But, urinary lactate dehydrogenase activity was not affected. Renal glutathione content of rat was significantly decreased in comparison with those of normal rat given bromate. Renal glutathione S-transferase and ${\gamma}$-glutamylcysteine synthetase activities were significantly decreased in bromate-treated group, but change in renal glutathione reductase activity was not significantly different from any other experimental group.

Effects of Pueraria thunbergiana Bentham Water Extracts on Hepatic Alcohol Metabolic Enzyme System In Rats (칡 열수추출물이 흰쥐의 알콜올 대사효소계에 미치는 영향)

  • 김명주;이정수;하오명;장주연;조수열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.1
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    • pp.92-97
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    • 2002
  • The effects of Pueraria flos (PF) and Pueraria radix (PR) water extract on the hepatic alcohol metabolic enzyme activities were examined in rats that were orally administered ethanol (25% v/v, 5g/kg body weight/day) for 5 weeks. The PF and PR water extract were supplemented in a diet, based on 1.2 g or 2.4 g of raw PF or PR/kg body weight/body. Alcohol administration without the PF or PR supplementation significantly decreased net weight gain, feed intake and feed efficiency ratio. However. both dose of the PF of PR supplementation resulted in significant enhancement of growth and suppression of increased relative weight of liver, brain and heart by alcohol administration. Activities of hepatic alcohol dehydrogenase and microsomal ethanol oxidizing system were higher in the alcohol treated group than in the normal group, while aldehyde dehydrogenase activity was significantly lowered in the alcohol treated group. The hepatic metabolic enzyme activities altered by alcohol administration were normalized by both doses of PF or PR supplement. Hepatic monoamine oxidase activity and hydrogen peroxide, which were significantly higher in the alcohol treated group than in the normal group, were also decreased by the supplementation with either PF or PR. These results indicate that low-or high-supplementation of either water extract PF or PR may alleviate ethanol-induced hepatotoxicity by altering alcohol metabolic enzyme activities.

Protective Effects of Ethanol Extract of Allium hookeri Root on Acute Alcohol-Induced Intoxication in ICR Mice (급성 알코올 독성을 유발한 ICR Mouse에서 Allium hookeri 뿌리 에탄올 추출물의 간 기능 보호 효과)

  • Kang, Hae-Young;Lee, Cho-Eun;Ly, Sun-Yung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.5
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    • pp.625-633
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    • 2016
  • Allium hookeri is known as a healthy food since it contains larger amounts of sulfur compounds than commonly known alliaceous plants. The antioxidant and anti-inflammatory effects of A. hookeri were compared between two types of extracts, $80^{\circ}C$ water and 95% ethanol extracts of A. hookeri roots. A. hookeri root 95% ethanol extracts displayed superior total polyphenol content, antioxidant activity [1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical scavenging activity], and anti-inflammation activity than those of water extracts (P<0.05). We studied the effects of A. hookeri root 95% ethanol extracts (95% ethanol extracts group: AHE) on acute alcohol-induced intoxication in mice. AHE [250, 500, and 1,000 mg/kg body weight (BW)/d] was orally administered to the study group once a day for 1 week. On the last day of AHE treatment, 40% ethanol (10 mL/kg BW) was orally administered to induce acute liver injury. The blood alcohol concentration of mice treated with AHE was significantly lower compared to the control group (P<0.05). The levels of hepatic aspartate aminotransferase and alanine aminotransferase were lower in the AHE-treated group than the control group (P<0.05). The RT-PCR results for alcohol dehydrogenase and aldehyde dehydrogenase measured based on mRNA in liver tissues showed that enzyme activities were higher in the AHE-treated group than in the control group at a low blood alcohol concentration.

α-Glucosidase, Tyrosinase, and Elastase Inhibitory Effects of Enzymatic Extracts from Ecklonia cava and its Alcohol Metabolizing Activity (감태(E. cava Kjellman) 효소분해산물의 항당뇨 및 알코올 분해능과 미용효과)

  • Kim, Hye-Youn;Cho, Eun-Kyung;Kang, Su-Hee;Bae, Jeong-Mi;Choi, Young-Ju
    • Journal of Life Science
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    • v.22 no.6
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    • pp.751-759
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    • 2012
  • Microbulbifer sp. was used to acquire the degrading products from Ecklonia cava (DPEC) and the products were investigated to determine the physiological activities. Firstly, 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity and superoxide dismutase (SOD) assay were about 84.1% and 89.6% at 2.5 mg/ml, respectively. In addition, nitrite scavenging ability was shown to be 56.3% at 0.5 mg/ml on pH 1.2. ${\alpha}$-Glucosidase inhibitory activity was increased in a dose-dependent manner and was about 58.7% at 2.5 mg/ml. To determine the influence of DPEC on alcohol metabolism, the generating activity of reduced-nicotinamide adenine dinucleotide (NADH) by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were measured. Facilitating rates of ADH and ALDH activities by DPEC were 123.3% and 215.2% at 2.5 mg/ml, respectively. For analyses of anti-wrinkling and whitening effects, its elastase and tyrosinase inhibitory activities were measured and were about 73.1% and 42.2% at 2.5 mg/ml, respectively. These results indicated that DPEC has valuable biological attributes owing to its antioxidant, nitrite scavenging, and alcohol metabolizing activities and ${\alpha}$-glucosidase, elastase, and tyrosinase inhibitory activities.