• Title/Summary/Keyword: Metabolism Induction

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Induction of Electrophilic Metabolites of PAH by Placental Microsomes in Mice (쥐의 태반조직에 의한 PAH 화합물의 대사활성화)

  • 김선희;조철오;신대현;박균하
    • The Korean Journal of Zoology
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    • v.31 no.2
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    • pp.142-146
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    • 1988
  • Metabolism of benzo(a)pyrene, the most thoroughly studied PAH, was studied in mouse placental microsomes incubated with $^3$H-labeled B(a)P. B(a)P metabolites were separated using HPLC fitted with a C18- $\mu$ Bondapak column. The single major metabolite by mouse placental microsomes induced by B(a)P was 7, 8-diol B(a)P, while 4, 5-diol B(a)P, 3-OH and quinones constituted minor metabolites. Treatment with 3-methyl-cholanthrene to mice resulted in indudion of hydroxy B(a)P and quinone compounds. Phenobarbital treated mouse placental microsomes also showed elevated level of B(a)P metabolism with 7, 8-diol B(a)P as a major metabolite.

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The Metabolism of (2-$^{14}C$) Mevalonic Acid on Photoperiodic Induction in Grafted Solanum Andigena

  • Bae, Moo;Mercer, E.I.
    • Nuclear Engineering and Technology
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    • v.2 no.2
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    • pp.73-84
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    • 1970
  • The metabolism of sterol precurosor in leaves of Salanum andigena grafted between photoinduced and noninduced plant was investigated with the use of (2-$^{14}$ C) mevalonic acid. By the technique of the preparative gas-liquid chromatography, radioactive compounds of squalene, 4,4’-dimethylsterols and 4-demethylsterol were isolated and determined quantitatively. When labeled mevalonic acid n as applied to leaves radioactivity was extensively incorporated into non-saponifiable materials of lipid fraction and aqueous fraction (ethanol-water fraction). Radioactivity of 14C derived from (2-$^{14}$ C) mevalonic acid was transmissible from photoinduced plant to non-induced plant across the graft union, as tuberization hormone was, and incorporated into the sterols of the non-induced plant. Inhibitors of sterol biosynthesis, SK & F 7997 and nicotinic acid, are effective suppressors of tuber growing, if applied to leaves during photoinduction period. The experimental results suggest that certain substance containing isoprene unit, or sterol-like compound may participate in tuber growing.

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MiT Family Transcriptional Factors in Immune Cell Functions

  • Kim, Seongryong;Song, Hyun-Sup;Yu, Jihyun;Kim, You-Me
    • Molecules and Cells
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    • v.44 no.5
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    • pp.342-355
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    • 2021
  • The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

Enrichment of Resveratrol Content in Harvested Grape using Modulation of Cell Metabolism with UV Treatment (수확 후 포도의 UV 처리 세포대사조절에 의한 레스베라트롤 함량 강화)

  • Cho, Yong-Jin;Maeng, Jin-Soo;Kim, Chong-Tai;Pyee, Jae-Ho
    • Journal of the East Asian Society of Dietary Life
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    • v.21 no.5
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    • pp.739-745
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    • 2011
  • This study was performed to investigate the enrichment of resveratrol content in harvested grapes using the modulation of cell metabolism with ultra-violet (UV) irradiation. Resveratrol, a phytoalexin, is produced by stilbene synthase (STSY) from malonyl-CoA and ${\rho}$-coumaroyl-CoA. Its biosynthesis has been reported to be induced by UV and other environmental factors. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that STSY Promoter 1 in grapes was very highly expressed by treatment with UV. Grapes were harvested and treated for post-harvest induction of STSY gene expression with UV, and then their resveratrol content was analyzed. UV treatment for 5 minutes provided the best condition for the induction of STSY gene expression. When harvested Gerbong and MBA grapes were treated with a prototype UV radiator, their resveratrol content was enriched upto 5 times compared with untreated grapes. These results suggest that a post-harvest UV treatment can be applied to enrich resveratrol content in grapes and add value to them.

EFFECT OF PHENOBARBITAL AND / OR SKF 525-A ON THE METABOLISM AND ACUTE TOXICITY OF PARATHION IN ADULT FEMALE PATS (자성 흰쥐의 파라치온 급성독성 및 대사에 미치는 페노바르비탈 및 SKF-525-A의 영향)

  • Choi, Jae-Hwa;Yim, Hye-Kyung;Kim, Young-Chul
    • Toxicological Research
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    • v.6 no.1
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    • pp.51-59
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    • 1990
  • Effects of altering hepatic mixed-function oxidase (MFO) enzyme activities on the metabolism and acute toxicity of parathio were investigated in adult female rats. In vitro hepatic metabolism of parathion to paraoxon was increased by phenobarbital pretreatment (50 mg/kg/day, ip, for 4 consecutive days) and SKF 525-A (50 mg/kg, ip, 1 hr prior to sacrifice) decreased paraoxon formation indicating that phenobarbital induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to paraoxon. Degradation of paraoxon to p-nitrophenol was increased by phenobarbital pretreatment, but not affected by SKF 525-A suggesting that MFO activities play only a minor role in the detoxification of the active metabolite of this insecticide. The phenobarbital-induced increase in paraoxon formation was partially antagonized by SKF 525-A. Significant activity for both parathion activation and paraoxon degradation was also observed in the lung preparation, however, this extrahepatic parathion and paraoxon metabolizing activity was not induced by phenobarbital or inhibited by SKF 525-A pretreatment. Phenobarbital pretreatment increased paraoxon level in livers of rats when measured 3 hr following parathion injection (2 mg/kg, ip). SKF 525-A did not alter parathion or paraoxon levels in brain, blood and liver. Phenobarbital pretreatment decreased the toxicity of parathion (4mg/kg, ip) or paraoxon (1.5 mg/kg, ip) as determined by decreases in lethality and inhibition of brain and lung acetylcholinesterases. An additional SKF 525-A treatment failed to decrease the protective effects of phenobarbital against parathion or paraoxon toxicity. These results suggest that some unknown factors other than hepatic MFO induction are involved in the protective action of phenobarbital against parathion and paraoxon toxicity.

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Alternating Acquisition Technique for Quantification of in vitro Hyperpolarized [1-13C] Pyruvate Metabolism

  • Yang, Seungwook;Lee, Joonsung;Joe, Eunhae;Lee, Hansol;Song, Ho-Taek;Kim, Dong-Hyun
    • Investigative Magnetic Resonance Imaging
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    • v.20 no.1
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    • pp.53-60
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    • 2016
  • Purpose: To develop a technique for quantifying the $^{13}C$-metabolites by performing frequency-selective hyperpolarized $^{13}C$ magnetic resonance spectroscopy (MRS) in vitro which combines simple spectrally-selective excitation with spectrally interleaved acquisition. Methods: Numerical simulations were performed with varying noise level and $K_p$ values to compare the quantification accuracies of the proposed and the conventional methods. For in vitro experiments, a spectrally-selective excitation scheme was enabled by narrow-band radiofrequency (RF) excitation pulse implemented into a free-induction decay chemical shift imaging (FIDCSI) sequence. Experiments with LDH / NADH enzyme mixture were performed to validate the effectiveness of the proposed acquisition method. Also, a modified two-site exchange model was formulated for metabolism kinetics quantification with the proposed method. Results: From the simulation results, significant increase of the lactate peak signal to noise ratio (PSNR) was observed. Also, the quantified $K_p$ value from the dynamic curves were more accurate in the case of the proposed acquisition method compared to the conventional non-selective excitation scheme. In vitro experiment results were in good agreement with the simulation results, also displaying increased PSNR for lactate. Fitting results using the modified two-site exchange model also showed expected results in agreement with the simulations. Conclusion: A method for accurate quantification of hyperpolarized pyruvate and the downstream product focused on in vitro experiment was described. By using a narrow-band RF excitation pulse with alternating acquisition, different resonances were selectively excited with a different flip angle for increased PSNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Baseline signals from neighboring resonances can be effectively suppressed to accurately quantify the metabolism kinetics.

Effect of Feeding Mixture of Soybean Peptides, L-Carnitine and Garcinia Cambogia Extract on Body Weight and Lipid Metabolism in Rats

  • Park, Ju-Yeon;Lee, Hee-Sun;Kim, Ju-Young;Lee, Jin-Hee;Lee, Kang-Pyo;Kim, Min-Sun;Kim, Yangha
    • Preventive Nutrition and Food Science
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    • v.11 no.3
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    • pp.210-217
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    • 2006
  • This study was performed to investigate effects of the experimental mixture containing soybean peptides, L-carnitine and Garcinia Cambogia extract on body weight and lipid metabolism in rats. Male Sprague-Dawley rats (n=40) of eight weeks old were raised for four weeks with high fat diet (40% fat as calorie) to induce obesity. After induction of obesity, rats were feed control (C) diet, containing either 0.16% (+1D), 1.6% (+10D), 8% (+50D) of experimental mixture for eight weeks. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity and total protein and albumin concentration were not different among groups. The Body weight gain was significantly lower in experimental mixture diet group compared to control group. Weights of perirenal fat pad and epididymal fat pad in the +50D group were significantly lower than those in the +1D and +10D groups. Plasma total lipid and liver total cholesterol levels in the experimental groups were significantly lower than those in the control group. Fecal total lipid and total cholesterol excretions were highest in +50D group. These results suggest that the experimental mixture containing peptides, L-carnitine and Garsinia Canbogia extract is effective for reducing the body weight and adipose tissue weight which may be due to the modulation of lipid metabolism and the increased fecal excretion of lipid.

Induction of cytochrome P450 2E1 by 1-bromopropane in male ICR mice (ICR 마우스 수컷에서 1-bromopropane에 의한 cytochrome P450 2E1의 유도)

  • Lee, Sang-Kyu;Jeong, Tae-Cheon
    • Environmental Analysis Health and Toxicology
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    • v.24 no.3
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    • pp.213-218
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    • 2009
  • 1-bromopropane (1-BP) has been used in numerous purposes such as an intermediate in the synthesis of pharmaceuticals, a solvent for fats, waxes, or resins and a substitute for chlorofluorocarbons that destroy the ozone layer. However, the studies related to the modulation of activities of hepatic cytochrome P450s (CYPs) are not reported yet. This study was the first study to investigate the potential effect for the activities of hepatic CYPs by the treatment of 1-BP in vivo. When 1-BP was treated to male ICR mice by dose-dependently at the dose levels of 200, 500 and 1,000 mg/kg of body weight once, the activity of CYP2E1 was selectively increased for 24 h. The inductive potency for the activity of CYP2E1 by 1-BP was equal to induction by acetone a well-known selective CYP2E1 inducer. The present results indicated that 1-BP would affect the metabolism of 1-BP itself and/or other xenobiotics.

Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species

  • Park, Bo-Yeon;Chung, Ja-Yong
    • Nutrition Research and Practice
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    • v.3 no.3
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    • pp.192-199
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    • 2009
  • Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ${\sim}2$-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism.

Regulatory Role of Autophagy in Globular Adiponectin-Induced Apoptosis in Cancer Cells

  • Nepal, Saroj;Park, Pil-Hoon
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.384-389
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    • 2014
  • Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.