• 제목/요약/키워드: endogenous zinc

검색결과 23건 처리시간 0.023초

Kaiso represses the expression of glucocorticoid receptor via a methylation-dependent mechanism and attenuates the anti-apoptotic activity of glucocorticoids in breast cancer cells

  • Zhou, Lin;Zhong, Yan;Yang, Fang-hui;Li, Zi-bo;Zhou, Jiang;Liu, Xie-hong;Li, Min;Hu, Fang
    • BMB Reports
    • /
    • 제49권3호
    • /
    • pp.167-172
    • /
    • 2016
  • Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely correlated with glucocorticoid receptor (GR) expression in breast carcinomas. Knockdown of Kaiso increased GR expression, while overexpression of Kaiso inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP experiments demonstrated that endogenous Kaiso was associated with the GR promoter sequence in a methylation-dependent manner. Since glucocorticoids inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti-apoptotic effects. We found that overexpression of Kaiso attenuated the anti-apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential therapeutic target in GC-combination chemotherapy in breast cancer.

DNA Cleavage Induced by the Reaction of Salsolinol with Cu,Zn-Superoxide Dismutase

  • Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
    • /
    • 제28권12호
    • /
    • pp.2329-2332
    • /
    • 2007
  • Salsolinol, endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the oxidative damage of DNA induced by the reaction of salsolinol with Cu,Zn-SOD. When plasmid DNA incubated with salsolinol and Cu,Zn-SOD, DNA cleavage was proportional to the concentrations of salsolinol and Cu,Zn-SOD. The salsolinol/Cu,Zn-SOD system-mediated DNA cleavage was significantly inhibited by radical scavengers such as mannitol, ethanol and thiourea. These results indicated that free radicals might participate in DNA cleavage by the salsolinol/Cu,Zn-SOD system. Spectrophotometric study using a thiobarbituric acid showed that hydroxyl radical formation was proportional to the concentration of salsolinol and was inhibited by radical scavengers. These results indicated that hydroxyl radical generated in the reaction of salsolinol with Cu,Zn-SOD was implicated in the DNA cleavage. Catalase and copper chelators inhibited DNA cleavage and the production of hydroxyl radicals. These results suggest that DNA cleavage is mediated in the reaction of salsolinol with Cu,Zn-SOD via the generation of hydroxyl radical by a combination of the oxidation reaction of salsolinol and Fenton-like reaction of free copper ions released from oxidatively damaged SOD.

Carbon Monoxide as a Novel Central Pyrogenic Mediator

  • Jang, Choon-Gon;Lee, Seung-Jin;Yang, Sang-In;Kim, Jin-Hak;Sohn, Uy-Dong;Lee, Seok-Yong
    • Archives of Pharmacal Research
    • /
    • 제25권3호
    • /
    • pp.343-348
    • /
    • 2002
  • Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. CO-saturated aCSF ($4{\;}{\mu}l$, i.c.v.) and hemin ($10{\;}{\mu}g$, i.c.v.) elicited marked febrile response. Pretreatment with indomethacin completely inhibited CO- and hemin-induced fever. Zinc protoporphyrin-IX ($10{\;}{\mu}g$, i.c.v.) or ODQ ($50{\;}{\mu}g$, i.c.v.) partially reduced hemin-induced febrile response. Dibutyryl-cGMP ($100{\;}{\mu}g$, i.c.v.) produced profound febrile response and this febrile response was attenuated by indomethacin. These results indicate that endogenous CO may have a role as a pyrogenic mediator in CNS and CO-mediated pyresis is dependent on prostaglandin production and partially on activation of soluble guanylate cyclase.

Effect of micronutritional-element deficienies on the metabolism of Chlorella cells. (I) -On the growth rate, respiation and photosynthesis- (Chlorella 의 물질대사에 미치는 미양원소의 결핍효과 1 (제 1 ) -생 및 광합성 에 관하여-)

  • Lee, Yung-Nok;Chin, Pyung;Sim, Woong-Seop
    • Korean Journal of Microbiology
    • /
    • 제5권1호
    • /
    • pp.15-19
    • /
    • 1967
  • Chlorella ellipsoidea cells were cultured in an iron, copper, zinc, manganese, molybdenum or boron-free medium. Physiological activities such as growth rate, reproduction, endogenous and glucose respiration, photosynthetic activity and biosythesis of chlorophyll of the micro-element definition cells were measured. It generally, growth rate, respiratory and photosynthetic activities, and biosynthesis of chlorophyll of the micro-element deficient cells decreased more or less, compared with those of the normal cells. The growth of the algal cells in an iron-free medium were retarded severely with the chlorosis, and the photosynthetic activity of the cells decreased remarkably even though the low content of chlorophyll in the cells owing to the iron-deficiency is considered. Therefore, it is deduced that iron takes part in the photosynthetic process itself, possibly by its participation in the photo phosphorylation coupled with electron transport. Respiratory activity of boron-deficient cells showed the most severe decrease whereas those of the molybdenum-deficient cells showed very slight decrease in spite of severe growth retardation.

  • PDF

Trace Metal Contents in Cultured and Wild fishes from the Coastal Area of Tongyeoung, Korea and their Safely Evaluations (통영연근해역 양식산 및 자연산 어류 중의 미량금속 함량 및 안전성 평가)

  • Choi Jong-Duck;Jeoung In-geon
    • Journal of Food Hygiene and Safety
    • /
    • 제20권4호
    • /
    • pp.205-210
    • /
    • 2005
  • The content of the trace metals in the cultured and wild fishes were determined. The tested fishes were genuin porgy (Pagrus major) and black porgy (Acanthopogrus schlegeli). The samples of the cultured and wild fishes were collected from slices of raw fish in shops, during 2003 to 2004. The samples were digested with acids, then analyzed by ICP (inductively Coupled plasma Spectrometer) and AAS (Automic Absorption Spectrometer) for the content of lead (Pb), cadmium (Cd), arsenic (As), copper (Cu), manganese (Mn) and zinc (Zn). The content of mercury (Hg) was determined using mercury analyzer. The mean contents of trace metals in cultured and wild fish was 0.031,0.047mg/kg far total-mercury,0.321,0.407 for Pb, 0.048,0.063 for Cd, 1.006, 1.132 for As, 0.467,0.806 for Cu, 0.233, 0.293 for Cr, 9.69, 12.20 for Zn,0.798, 0.624 mg/kg far Mn, respectively. The content of all the trace metals except manganese in wild fish was more than that in cultured fish. The highest level of total-mercury, lead, cadmium, zinc, chromium and arsenic in the samples analyzed were all below the quarantine limit of Korean regulation and guideline established by the U.S. Food and Drug Administration f3r human consumption. The level of the trace metals in the samples was negligible, which could be endogenous. Our data obtained in this study showed that the average weekly intakes of lead, cadmium and mercury from cultured and wild fishes takes about $6\∼13\%$ of Un(Provisional Tolerance Weekley Intakes) that FAO/WHO Joint Food Additive and Contaminants Committee has set to evaluate their safeties.

Issues pertaining to Mg, Zn and Cu in the 2020 Dietary Reference Intakes for Koreans

  • Chung, Hae-Yun;Lee, Mi-Kyung;Kim, Wookyoung;Choi, Mi-Kyeong;Kim, Se-Hong;Kim, Eunmee;Kim, Mi-Hyun;Ha, Jung-Heun;Lee, Hongmie;Bae, Yun-Jung;Kwun, In-Sook
    • Nutrition Research and Practice
    • /
    • 제16권sup1호
    • /
    • pp.113-125
    • /
    • 2022
  • In the current years, it has now become necessary to establish standards for micronutrient intake based on scientific evidence. This review discusses issues related to the development of the 2020 Dietary Reference Intakes for Koreans (KDRI) for magnesium (Mg), zinc (Zn), and copper (Cu), and future research directions. Following issues were encountered when establishing the KDRI for these minerals. First, characteristics of Korean subjects need to be applied to estimate nutrient requirements. When calculating the estimated average requirement (EAR), the KDRI used the results of balance studies for Mg absorption and factorial analysis for Zn, which is defined as the minimum amount to offset endogenous losses for Zn and Mg. For Cu, a combination of indicators, such as depletion/repletion studies, were applied, wherein all reference values were based on data obtained from other countries. Second, there was a limitation in that it was difficult to determine whether reference values of Mg, Zn, and Cu intakes in the 2020 KDRI were achievable. This might be due to the lack of representative previous studies on intakes of these nutrients, and an insufficient database for Mg, Zn, and Cu contents in foods. This lack of database for mineral content in food poses a problem when evaluating the appropriateness of intake. Third, data was insufficient to assess the adequacy of Mg, Zn, and Cu intakes from supplements when calculating reference values, considering the rise in both demand and intake of mineral supplements. Mg is more likely to be consumed as a multi-nutrient supplement in combination with other minerals than as a single supplement. Moreover, Zn-Cu interactions in the body need to be considered when determining the reference intake values of Zn and Cu. It is recommended to discuss these issues present in the 2020 KDRI development for Mg, Zn, and Cu intakes in a systematic way, and to find relevant solutions.

HO-1 Induced by Cilostazol Protects Against TNF-${\alpha}$-associated Cytotoxicity via a PPAR-${\gamma}$-dependent Pathway in Human Endothelial Cells

  • Park, So-Youn;Bae, Jin-Ung;Hong, Ki-Whan;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제15권2호
    • /
    • pp.83-88
    • /
    • 2011
  • A large body of evidence has indicated that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In our previous study, cilostazol was found to increase the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) in synovial cells. Thus, the present study was undertaken to examine whether cilostazol is able to counteract tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced cell death in endothelial cells via the induction of HO-1 expression. We exposed human umbilical vein endothelial cells (HUVECs) to TNF-${\alpha}$ (50 ng/ml), with or without cilostazol ($10{\mu}M$). Pretreatment with cilostazol markedly reduced TNF-${\alpha}$-induced viability loss in the HUVECs, which was reversed by zinc protoporphyrine IX (ZnPP), an inhibitor of HO-1. Moreover, cilostazol increased HO-1 protein and mRNA expression. Cilostazol-induced HO-1 induction was markedly attenuated not only by ZnPP but also by copper-protoporphyrin IX (CuPP). In an assay measuring peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) transcription activity, cilostazol directly increased PPAR-${\gamma}$ transcriptional activity which was completely abolished by HO-1 inhibitor. Furthermore, increased PPAR-${\gamma}$ activity by cilostazol and rosiglitazone was completely abolished in cells transfected with HO-1 siRNA. Taken together, these results indicate that cilostazol up-regulates HO-1 and protects cells against TNF-${\alpha}$-induced endothelial cytotoxicity via a PPAR-${\gamma}$-dependent pathway.

High Performance Liquid Chromatographic Assay of a New Fluoroquinolone, LB20304, in the Plasma of Rats and Dogs

  • Seo, Mi-Kyeong;Jeong, Yi-Na;Kim, Hoon-Joo;Kim, In-Chull;Lee, Yong-Hee
    • Archives of Pharmacal Research
    • /
    • 제19권6호
    • /
    • pp.554-558
    • /
    • 1996
  • High-performance liquid chromatographic method was developed for the determination or LB 20304 (compound 1) in the plasma of rats and dogs. The analyte was deproteinized with 1 volume of methanol and 1/2 volume of 10% zinc sulfate, and the supernatant was injected onto a reversed-phase HPLC column. The mobile phase was a mixture of 24 parts of acetonitrile and 76 parts of 0.1% trifluoroacetic acid. The flow rate was 1 ml/min, and the effluent was monitored by fluorescence detector at an excitation wavelength of 337 nm and an emission wavelength of 460 nm. The retention time of compound 1 was 6.3 min. The assay of compound 1 was linear over the concentration range of 0.2-100.mu.g/ml in the plasma of rats and dogs. The lower limit of quantification was 0.2.mu.g/ml using 100.mu.l of plasma with a 97-99% accuracy and a 12-14% precision. In the 0.5, 5, and 50.mu.g/ml quality control samples, the intra- and inter-day accuracy were 88-95% and 88-97%, whereas intra- and interday precision were 0.5-6.6% and 0.2-9.3%, respectively, in the plasma of rats and dogs. The recoveries were 68-71% independent of concentration and species in the plasma. No interferences from endogenous substances were observed. Taken together, the above HPLC assay method by deproteinization and fluorescence detection was suitable for the determination of compound 1 in the preclinical pharmacokinetics.

  • PDF

Expression of Egr3 in mouse gonads and its localization and function in oocytes

  • Shin, Hyejin;Seol, Dong-Won;Nam, Minyeong;Song, Haengseok;Lee, Dong Ryul;Lim, Hyunjung Jade
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제30권6호
    • /
    • pp.781-787
    • /
    • 2017
  • Objective: The early growth response (Egr) family consists of four members (Egr1, Egr2, Egr3, and Egr4) that are zinc finger transcription factors. Among them, Egr3 is involved in transcriptional regulation of target genes during muscle spindle formation and neurite outgrowth. We previously showed that the immunoreactive Egr3 is localized on oocyte spindle and accumulate near the microtubule organizing center during meiosis I in mice. Egr3 was also shown to be localized on spermatocytes. We herein investigated if Egr3 is expressed in mouse gonads and if Egr3 blockade results in any defect in oocyte maturation. Methods: Expression of Egr3 in mouse gonads was examined by reverse transcription-polymerase chain reaction. Full-length Egr3 and truncated Egr3 (${\Delta}Egr3$) complementary RNAs (cRNAs) with Xpress tag at N-terminus and DsRed2 at C-terminus, and small interfering RNA (siRNA) targeting Egr3 were microinjected into mouse oocytes at germinal vesicle stage. Localization of microinjected Egr3 was examined by confocal live imaging and immunofluorescence staining. Results: Egr3 mRNA was detected in mouse ovaries and testes from 1 to 4 week-old mice. An uncharacterized longer transcript containing 5'untranslated region was also detected in 3 and 4 week-old gonads. Microinjected Xpress-Egr3-DsRed2 or Xpress-${\Delta}Egr3$-DsRed2 localized to nuclei and chromosomes during meiotic progression. Microinjection of these cRNAs or Egr3 siRNA in oocytes did not affect meiotic maturation. Immunofluorescence staining of Egr3 in Xpress-${\Delta}Egr3$-DsRed2-injected oocytes showed a positive signal only on meiotic spindle, suggesting that this antibody does not detect endogenous or exogenous Egr3 in mouse oocytes. Conclusion: The results show that Egr3 localizes to chromosomes during meiotic progression and that certain antibodies may not faithfully represent localization of target proteins in oocytes. Egr3 seems to be dispensable during oocyte maturation in mice.

Effects of chemical additives and heat treatment on the baking properties of wheat flour dough (화학 첨가제와 밀가루의 열처리가 제빵 특성에 미치는 효과)

  • 이지은;고봉경
    • Korean journal of food and cookery science
    • /
    • 제20권2호
    • /
    • pp.119-125
    • /
    • 2004
  • Effects of various chemical additives and heat treatments were investigated on the wheat flour doughs and breads. Ammonium ferric citrate, Ca-citrate, CaCl$_2$, FeSO$_4$, MgCl$_2$and ZnO were mixed respectively to the flour up to 0.1% of flour dry weight basis. Ammonium ferric citrate and ferric sulfate showed no significant effects on the dough properties and magnesium sulfate, calcium chloride and zinc oxide increased elastic properties and optimum dough mixing time. However, calcium citrate and magnesium chloride showed no significant effects on the dough mixing properties. Most of chemicals were detrimental on the bread volume except MgSO$_4$ and CaCl$_2$. Breads with MgSO$_4$ and CaCl$_2$ retained the equal or slightly higher volume compared to control bread. Crumb and crust colors of breads with addition of chemicals were changed to lighter than that of control bread. L values both of crumb and crust increased with addition of chemicals except Ca-citrate. To inactivate the endogenous enzymes of flour, flour was roasted under electric oven, exposed to UV and microwave. Those heat treatments of flour increased dough stability and produced no dough breakdown after optimum mixing time. However, bread volume of heat-treated flour decreased.