• 제목/요약/키워드: DNA-dependent

검색결과 1,346건 처리시간 0.026초

Bioproduction and Anticancer Activity of Biosurfactant Produced by the Dematiaceous Fungus Exophiala dermatitidis SK80

  • Chiewpattanakul, Paramaporn;Phonnok, Sirinet;Durand, Alain;Marie, Emmanuelle;Thanomsub, Benjamas Wongsatayanon
    • Journal of Microbiology and Biotechnology
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    • 제20권12호
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    • pp.1664-1671
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    • 2010
  • A new biosurfactant producer was isolated from palm-oil-contaminated soil and later identified through morphology and DNA sequencing as the yeast-like fungus Exophiala dermatitidis. Biosurfactant production was catalyzed by vegetable oil, supplemented with a basal medium. The culture conditions that provided the biosurfactant with the highest surface activity were found to be 5% palm oil with 0.08% $NH_4NO_3$, at a pH of 5.3, with shaking at 200 rpm, and a temperature of $30^{\circ}C$ for a 14-day period of incubation. The biosurfactant was purified, in accordance with surfactant properties, by solvent fractionation using silica gel column chromatography. The chemical structure of the strongest surface-active compound was elucidated through the use of NMR and mass spectroscopy, and noted to be monoolein, which then went on to demonstrate antiproliferative activity against cervical cancer (HeLa) and leukemia (U937) cell lines in a dose-dependent manner. Interestingly, no cytotoxicity was observed with normal cells even when high concentrations were used. Cell and DNA morphological changes, in both cancer cell lines, were observed to be cell shrinkage, membrane blebbling, and DNA fragmentation.

Glucosylated Polyethylenimine as a Tumor-Targeting Gene Carrier

  • Park In-Kyu;Cook Seung-Eun;Kim You-Kyoung;Kim Hyun-Woo;Cho Myung-Haing;Jeong Hwan-Jeong;Kim Eun-Mi;Nah Jae-Woon;Bom Hee-Seung;Cho Chong-Su
    • Archives of Pharmacal Research
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    • 제28권11호
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    • pp.1302-1310
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    • 2005
  • Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-$\%$) had no cytotoxic effect on cells even at polymer concentrations higher than 200 $\mu$g/mL. Compared to unglucosylated PEl. glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEI. Gamma imaging technique revealed GPEI/DNA complex was distributed in liver. spleen. and tumors.

Anti-oxidant Effect of Agastache rugosa on Oxidative Damage Induced by $H_2O_2$ in NIH 3T3 Cell

  • Hong, Se-Chul;Jeong, Jin-Boo;Park, Gwang-Hun;Kim, Jeong-Sook;Seo, Eul-Won;Jeong, Hyung-Jin
    • 한국자원식물학회지
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    • 제22권6호
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    • pp.498-505
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    • 2009
  • The plant Agastache rugosa Kuntze has various physiological and pharmacological activities. Especially, it has been regarded as a valuable source for the treatment of anti-inflammatory and oxidative stress-induced disorders. However, little has been known about the functional role of it on oxidative damage in mammalian cells by ROS. In this study, we investigated the DPPH radical, hydroxyl radical, hydrogen peroxide and intracellular ROS scavenging capacity, and $Fe^{2+}$ chelating activity of the extracts from Agastache rugosa. In addition, we evaluated whether the extract can be capable of reducing $H_2O_2$-induced DNA and cell damage in NIH 3T3 cells. These extracts showed a dose-dependent free radical scavenging capacity and a protective effect on DNA damage and the lipid peroxidation causing the cell damage by $H_2O_2$. Therefore, these results suggest that Agastache rugosa is useful as a herbal medicine for the chemoprevention against oxidative carcinogenesis.

HIF-1α-Dependent Gene Expression Program During the Nucleic Acid-Triggered Antiviral Innate Immune Responses

  • Hong, Sun Woo;Yoo, Jae Wook;Kang, Hye Suk;Kim, Soyoun;Lee, Dong-ki
    • Molecules and Cells
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    • 제27권2호
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    • pp.243-250
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    • 2009
  • Recent studies suggest a novel role of $HIF-1{\alpha}$ under nonhypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers $HIF-1{\alpha}$ activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of $HIF-1{\alpha}$ protein level as well as the increase in $HIF-1{\alpha}$ target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated $HIF-1{\alpha}$ knock-down. Interestingly, $HIF-1{\alpha}$ knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that $HIF-1{\alpha}$ activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.

Ubiquitin E3 ligases controlling p53 stability

  • Lee, Seong-Won;Seong, Min-Woo;Jeon, Young-Joo;Chung, Chin-Ha
    • Animal cells and systems
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    • 제16권3호
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    • pp.173-182
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    • 2012
  • The p53 protein plays a pivotal role in tumor suppression. The cellular level of p53 is normally kept low by proteasome-mediated degradation, allowing cell cycle progression and cell proliferation. Under stress conditions, such as DNA damage, p53 is stabilized and activated through various post-translational modifications of itself as well as of its regulatory proteins for induction of the downstream genes responsible for cell cycle arrest, DNA repair, and apoptosis. Therefore, the level of p53 should be tightly regulated for normal cell growth and for prevention of the accumulation of mutations in DNA under stress conditions, which otherwise would lead to tumorigenesis. Since the discovery of Mdm2, a critical ubiquitin E3 ligase that destabilizes p53 in mammalian cells, nearly 20 different E3 ligases have been identified and shown to function in the control of stability, nuclear export, translocation to chromatin or nuclear foci, and oligomerization of p53. So far, a large number of excellent reviews have been published on the control of p53 function in various aspects. Therefore, this review will focus only on mammalian ubiquitin E3 ligases that mediate proteasome-dependent degradation of p53.

Sclerotiorin: a Novel Azaphilone with Demonstrated Membrane Targeting and DNA Binding Activity against Methicillin-Resistant Staphylococcus aureus

  • Dasagrandhi, Chakradhar;Pandith, Anup;Imran, Khalid
    • 한국미생물·생명공학회지
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    • 제48권4호
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    • pp.429-438
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    • 2020
  • The emergence of multi-drug resistant, pathogenic methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health and has created a need for novel functional therapeutic agents. In this study, we evaluated the underlying mechanisms of the anti-MRSA effect of an azaphilone pigment, sclerotiorin (SCL) from Penicillium sclerotiorum. The antimicrobial activity of SCL was evaluated using agar disc diffusion, broth microdilution, time-kill assays and biophysical studies. SCL exhibits selective activity against Gram positive bacteria including MRSA (range, MIC = 128-1028 ㎍/ml) and exhibited rapid bactericidal action against MRSA with a > 4 log reduction in colony forming units within three hours of administration. Biophysical studies, using fluorescent probes and laser or electron microscopy, demonstrated a SCL dose-dependent alternation in membrane potential (62.6 ± 5.0.4% inhibition) and integrity (> 95 ± 2.3%), and the release of UV260 absorbing materials within 60 min (up to 3.2 fold increase, p < 0.01) of exposure. Further, SCL localized to the cytoplasm and hydrolyzed plasmid DNA. While in vitro checkerboard studies revealed that SCL potentiated the antimicrobial activity of topical antimicrobials such as polymixin, neomycin, and bacitracin (Fractional Inhibitory Concentration Index range, 0.26-0.37). Taken together these results suggest that SCL targets the membrane and DNA of MRSA to facilitate its anti-MRSA antimicrobial effect.

Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism

  • Jeong, Seung Min;Haigis, Marcia C.
    • Molecules and Cells
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    • 제38권9호
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    • pp.750-758
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    • 2015
  • Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

Regulation of Cycloinulooligosaccharide Fructanotransferase Synthesis in Bacillus macerans and Bacillus subtilis

  • Kim, Hwa-Young;Choi, Yong-Jin
    • Journal of Microbiology and Biotechnology
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    • 제10권6호
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    • pp.877-880
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    • 2000
  • Cycloinulooligosaccharide fructanotransferase (CFTase) converts inulin into cyclooligosaccharides consisting of six to eight molecules $\beta$-($2\rightarrow1$)-linked cyclic D-fructofuranose through intramolecular transfructosylation. We have examined the regulation of CFTase synthesis in Bacillus macerans and Bacillus subtilis. Synthesis of the CFTase was induced by inulin and it was subject to carbon catabolite repression (CCR) by glucose in both microorganisms. The DNA sequence upstream of the promoter of the CFTase gene was not involved in the inulin induction and glucose repression of the CFTase gene expression in B. subtilis. This suggests that the DNA element(s) responsible for the inuline induction and glucose repression is located downstream of the promoter region. Unexpectedly, the CCR of the expression of CFTase gene was observed not to be dependent on CcpA protein in B. subtilis.

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Antioxidative Activity of the Extracts from the Leaves and Fruits of Acer ginnala

  • Chung, Jin-Su;Lee, Min-Sun;Chung, Ji-Youn
    • Natural Product Sciences
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    • 제7권2호
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    • pp.45-48
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    • 2001
  • The antioxidative effect of the extracts from the leaves and fruits of Acer ginnala against free radicals was studied by two different methods using DPPH radical-generating system, and hydroxyl radical-generating system $(Cu^{++}/H_2O_2\;system)$ which induces DNA strand breaking. Compared with well known antioxidative plants, green tea, Scutellaria baicalensis, the Acer ginnala extracts showed excellent radical-scavenging activity in DPPH radical-generating system and inhibited effectively hydroxyl radical induced-DNA strand breaking in a concentration-dependent manner in $Cu^{++}/H_2O_2$ system whereas the green tea extract stimulated the strand breaking at a low concentration. These results suggest that he extracts from the leaves and fruits of Acer ginnula could be good antioxidative agents.

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가감형방지황탕 열수 추출물이 항산화 작용에 미치는 영향 (Antioxidant Property of the Gagam-Hyungbang-Gihwang-tang Using Biochemical Markers of Carcinogenesis)

  • 한진수;박성식
    • 대한한의학회지
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    • 제26권3호
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    • pp.204-214
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    • 2005
  • Objectives : The verity extract of the Gagam-Hyungbang-Gihwang-tang (GHG) was assessed to determine the mechanisms of its antioxidant activity. Methods : The fellowing effects were measured : GHG exhibited a concentration-treatment; scavenging ${\alpha},\;{\alpha}-diphenyl-\beta-picrylhydrazyl$ (DPPH) radical, linoleic acid oxidation in a thiocyanate assay system, and superoxide anion, hydroxyl radical-induced DNA nicking. We investigated mRNA levels such as superoxide-dismutase. Results : The GHG extract showed dose-dependent free radical scavenging activity, including DPPH radicals, hydroxyl radicals, and superoxide anion, using different systems. The GHG was also found to be effective in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals in Fenton's reaction mixture. Furthermore, SOD-1 mRNA expression levels increased in tat hepatoma H4IIE cells Conclusions : We expect that GHG will to helpful to the development of antioxidant activity treatments.

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