Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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  • Article
    Citation - WoS: 38
    Citation - Scopus: 47
    Docetaxel/Zoledronic Acid Combination Triggers Apoptosis Synergistically Through Downregulating Antiapoptotic Bcl-2 Protein Level in Hormone-Refractory Prostate Cancer Cells
    (John Wiley and Sons Inc., 2009) Karabulut, B.; Erten, C.; Gül, M. K.; Cengiz, E.; Karaca, B.; Küçükzeybek, Y.; Görümlü, G.; Atmaca, H.; Uzunoğlu, S.; Şanlı, U. A.; Baran, Yusuf; Uslu, R.
    Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.
  • Article
    Citation - WoS: 23
    Citation - Scopus: 29
    Physical Properties of Biopolymers Containing Natamycin and Rosemary Extract
    (John Wiley and Sons Inc., 2009) Türe, Hasan; Özen, Fatma Banu; Eroğlu, Erdal; Soyer, Ferda; Özen, Banu; Soyer, Ferda
    Antifungal biopolymers were prepared by incorporating natamycin (NA) and NA + rosemary extract (RE) into wheat gluten (WG) and methyl cellulose (MC) films. Interaction between antimicrobial agents and biopolymers was determined with mid-infrared spectroscopy and scanning electron microscopy (SEM). Water vapour permeability and mechanical properties of these films were also measured. Mid-infrared spectroscopy did not indicate any interaction. SEM observations showed that NA crystallises at high concentrations in biopolymers. There were no significant changes in water vapour permeabilities of biopolymers containing active agents at P < 0.05. While NA incorporation did not result in any changes in mechanical properties of WG films a reduction in tensile strength was observed for MC films containing high concentration of NA. In general, active agent incorporation into WG and MC films did not result in any considerable changes in their physical properties that could affect their application.
  • Article
    Citation - WoS: 73
    Citation - Scopus: 78
    Functional Analysis of Free Methionine-R Reductase From Saccharomyces Cerevisiae
    (American Society for Biochemistry and Molecular Biology, 2009) Le, Dung Tien; Lee, Byung Cheon; Marino, Stefano M.; Zhang, Yan; Fomenko, Dmitri E.; Kaya, Alaattin; Hacıoğlu, Elise; Kwak, Geun-Hee; Koç, Ahmet; Kim, Hwa-Young; Gladyshev, Vadim N.
    Methionine sulfoxide reductases (Msrs) are oxidoreductases that catalyze thiol-dependent reduction of oxidized methionines. MsrA and MsrB are the best known Msrs that repair methionine S-sulfoxide (Met-S-SO) and methionine-R-sulfoxide (Met-R-SO) residues in proteins, respectively. In addition, an Escherichia coli enzyme specific for free Met-R-SO, designated fRMsr, was recently discovered. In this work, we carried out comparative genomic and experimental analyses to examine occurrence, evolution, and function of fRMsr. This protein is present in single copies and two mutually exclusive subtypes in about half of prokaryotes and unicellular eukaryotes but is missing in higher plants and animals. A Saccharomyces cerevisiae fRMsr homolog was found to reduce free Met-R-SO but not free Met-S-SO or dabsyl-Met-R-SO. fRMsr was responsible for growth of yeast cells on Met-R-SO, and the double fRMsr/MsrA mutant could not grow on a mixture of methionine sulfoxides. However, in the presence of methionine, even the triple fRMsr/MsrA/MsrB mutant was viable. In addition, fRMsr deletion strain showed an increased sensitivity to oxidative stress and a decreased life span, whereas overexpression of fRMsr conferred higher resistance to oxidants. Molecular modeling and cysteine residue targeting by thioredoxin pointed to Cys101 as catalytic and Cys125 as resolving residues in yeast fRMsr. These residues as well as a third Cys, resolving Cys91, clustered in the structure, and each was required for the catalytic activity of the enzyme. The data show that fRMsr is the main enzyme responsible for the reduction of free Met-R-SO in S. cerevisiae.
  • Article
    Citation - WoS: 106
    Citation - Scopus: 114
    Msrb1 (methionine-R Reductase 1) Knock-Out Mice: Roles of Msrb1 in Redox Regulation and Identification of a Novel Selenoprotein Form
    (American Society for Biochemistry and Molecular Biology, 2009) Fomenko, Dmitri E.; Novoselov, Sergey V.; Natarajan, Sathish Kumar; Lee, Byung Cheon; Koç, Ahmet; Carlson, Bradley A.; Lee, Tae- Hyung; Kim, Hwa-Young; Hatfield, Dolph L.; Gladyshev, Vadim N.
    Protein oxidation has been linked to accelerated aging and is a contributing factor to many diseases. Methionine residues are particularly susceptible to oxidation, but the resulting mixture of methionine R-sulfoxide (Met-RO) and methionine S-sulfoxide (Met-SO) can be repaired by thioredoxin-dependent enzymes MsrB and MsrA, respectively. Here, we describe a knock-out mouse deficient in selenoprotein MsrB1, the main mammalian MsrB located in the cytosol and nucleus. In these mice, in addition to the deletion of 14-kDa MsrB1, a 5-kDa selenoprotein form was specifically removed. Further studies revealed that the 5-kDa protein occurred in both mouse tissues and human HEK 293 cells; was down-regulated by MsrB1 small interfering RNA, selenium deficiency, and selenocysteine tRNA mutations; and was immunoprecipitated and recognized by MsrB1 antibodies. Specific labeling with 75Se and mass spectrometry analyses revealed that the 5-kDa selenoprotein corresponded to the C-terminal sequence of MsrB1. The MsrB1 knock-out mice lacked both 5- and 14-kDa MsrB1 forms and showed reduced MsrB activity, with the strongest effect seen in liver and kidney. In addition, MsrA activity was decreased by MsrB1 deficiency. Liver and kidney of the MsrB1 knock-out mice also showed increased levels of malondialdehyde, protein carbonyls, protein methionine sulfoxide, and oxidized glutathione as well as reduced levels of free and protein thiols, whereas these parameters were little changed in other organs examined. Overall, this study established an important contribution of MsrB1 to the redox control in mouse liver and kidney and identified a novel form of this protein.
  • Article
    Citation - WoS: 12
    Citation - Scopus: 18
    Hematoprotective Effect of Seleno-L on Cyclophosphamide Toxicity in Rats
    (Taylor and Francis Ltd., 2009) Ayhancı, Adnan; Yaman, Suzan; Appak, Sıla; Güneş, Sibel
    Cyclophosphamide (CP) is a widely used antineoplastic drug that causes toxicity in the normal cell due to its metabolites. The major drawback of this drug is an undesirable myelosuppression. Selenium (Se) is a potent nutritional antioxidant that carries out biological effects by its incorporation into selenoproteins, such as glutathione peroxidase (GPx). The possible protective effects of seleno-l-methionine (SLM) against CP-related toxicity of blood cells and bone marrow of rats were investigated in this study. Intraperitoneal (i.p) administration of 50, 100, or 150mg/kg of CP caused, in a dose-dependent manner, reductions in the number of leukocytes (78, 89, and 92%, respectively), thrombocytes (22, 33, and 52%, respectively), and bone marrownucleated cells (72, 90, and 94%, respectively). The groups that had CP treatment alone were killed 3 days after the CP injection. For the groups having CPSLM, SLM (0.4 or 0.8mg/kg i.p) administration was started 3 days earlier than the CP administration and continued to the end of the experiment (6 days). On day 4, the animals were weighed again, relative doses of CP were estimated, and CPSLM was administered together. On day 7, blood samples were collected and bone marrow of animals were resected under anesthesia. The results indicated that treatment of rats within a select dose range of SLM could reduce CP-induced toxicity on blood cells and bone marrow.
  • Article
    Citation - WoS: 14
    Citation - Scopus: 23
    Water-Soluble Antioxidant Potential of Turkish Pepper Cultivars
    (American Society for Horticultural Science, 2008) Frary, Anne; Keçeli, Mehmet Ali; Ökmen, Bilal; Şığva, Hasan Özgür; Yemenicioğlu, Ahmet; Doğanlar, Sami
    In this work, 29 pepper cultivars that represent the diversity of types and varieties grown in Turkey were analyzed for water-soluble antioxidant capacity and phenolic and vitamin C contents. In addition, 14 non-Turkish cultivars were tested for comparison. Significant diversity was observed in the different cultivars with the most variation (7.4-fold) seen for total antioxidant capacity, which ranged from 2.57 to 18.96 mmol Trolox/kg. Vitamin C content for the peppers ranged from 522 to 1631 mg·kg-1, a 3.1-fold difference, whereas total phenolic content for the pepper cultivars ranged from 607 to 2724 mg·kg-1, a 4.5-fold difference. When cultivars were grouped by morphology/ use, it was found that some types had significantly more variation and higher antioxidant activities than other types. Thus, for water-soluble antioxidant capacity, most variation was seen in long, blunt-ended Çarliston types, whereas long, pointed Sivri peppers had the highest mean capacity. Bell-shaped Dolmalik and Sivri peppers had the most variation for phenolic content, but fancy Süs and Sivri types had the highest means for this trait. Dolmalik types showed the most variation for vitamin C content, whereas Süs and Sivri peppers had the highest means for this character. All three parameters were significantly and positively correlated with the strongest correlation between total antioxidant capacity and phenolic content (r = 0.71). The presence of significant variation for antioxidant content in Turkish germplasm indicates that this material can be used for improvement and genetic mapping of nutritional content in pepper.
  • Article
    Citation - Scopus: 2
    Identification of Potato Y Potyvirus (pvy°) Resistance in Wild and Cultivated Tomatoes
    (Türkiye Klinikleri Journal of Medical Sciences, 2009) Çelebi Toprak, Fevziye; Barutçu, Eminur; Frary, Anne; Doğanlar, Sami
    Potato Y potyvirus (PVY) is an important plant pathogen worldwide that infects and causes yield losses in the family Solanaceae including potato (Solarium tuberosum), pepper (Capsicum spp.), tomato (S. lycopersicum), and tobacco (Nicotiana tabacum). In this study, 20 different tomato accessions representing 6 different species were mechanically inoculated with PVY°. The plants were scored visually for symptoms and then tested for presence of the virus 2-4 weeks after inoculation by ELISA. The results were variable. Most wild species of tomato sustained PVY° replication in inoculated leaves. Some of the wild species showed an immune response, while some became systemically infected. Inoculation and analysis of F2 populations suggested that the resistance is controlled by a single recessive gene in different wild species.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Regulation of Mrna Stability Through a Pentobarbital-Responsive Element
    (Elsevier Ltd., 2007) Akgül, Bünyamin; Tu, Chen-Pei D.
    Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is intrinsically very labile. But exposure to pentobarbital renders it stabilized beyond what can be attributed to transcriptional activation. We aim here to identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's pentobarbital-mediated stabilization. In the context of hsp70 5′UTR and the 3′UTR of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same context of heterologous UTRs, we can reconstitute using the full-length gstD21 sequence the inherent instability of gstD21 mRNA and its stabilization by pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit decay intermediates lacking 3′UTR, which are not stabilized by PB treatment. The 3′UTR sequence, when inserted downstream from a reporter transcript, stabilizes it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests a polysome-associated decay pattern. We propose a regulatory model that features a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3′UTR of gstD21 mRNA.
  • Article
    Citation - WoS: 36
    Citation - Scopus: 46
    Expression of Vitreoscilla Hemoglobin in Gordonia Amarae Enhances Biosurfactant Production
    (Springer Verlag, 2006) Doğan, İlhan; Pagilla, Krishna R.; Webster, Dale A.; Stark, Benjamin C.
    The gene (vgb) encoding Vitreoscilla (bacterial) hemoglobin (VHb) was electroporated into Gordonia amarae, where it was stably maintained, and expressed at about 4 nmol VHb g -1 of cells. The maximum cell mass (OD 600) of vgb-bearing G. amarae was greater than that of untransformed G. amarae for a variety of media and aeration conditions (2.8-fold under normal aeration and 3.4-fold under limited aeration in rich medium, and 3.5-fold under normal aeration and 3.2-fold under limited aeration in mineral salts medium). The maximum level of trehalose lipid from cultures grown in rich medium plus hexadecane was also increased for the recombinant strain, by 4.0-fold in broth and 1.8-fold in cells under normal aeration and 2.1-fold in broth and 1.4-fold in cells under limited aeration. Maximum overall biosurfactant production was also increased in the engineered strain, by 1.4-fold and 2.4-fold for limited and normal aeration, respectively. The engineered strain may be an improved source for producing purified biosurfactant or an aid to microorganisms bioremediating sparingly soluble contaminants in situ.
  • Article
    Citation - WoS: 46
    Citation - Scopus: 52
    Antifungal Activity of Biopolymers Containing Natamycin and Rosemary Extract Against Aspergillus Niger and Penicillium Roquefortii
    (John Wiley and Sons Inc., 2008) Türe, Hasan; Eroğlu, Erdal; Soyer, Ferda; Özen, Fatma Banu
    Antimicrobial agent-releasing films have been proposed as an effective way of inhibiting chiefly surface spoilage of food products. Antifungal activities of natamycin (NA), rosemary extract (RE) and NA + RE were tested against Aspergillus niger and Penicillium roquefortii with agar disc diffusion assay. NA, RE and NA + RE were also included into biopolymers made from gluten and methyl cellulose. Minimum inhibitory concentrations (MIC) of NA in both films were 2 and 1 mg NA per 10 g film solution against A. niger and P. roquefortii, respectively. RE did not show any inhibitory antifungal activity alone. Although NA incorporated into both films at a concentration of 1.5 mg NA per 10 g film solution was not effective against A. niger, combination of NA at the same concentration with RE in the films inhibited the growth of this mould. NA in solution or in biopolymers is very effective in inhibiting the growth of selected organisms, and RE acted synergistically with NA to prevent the growth of A. niger when incorporated into both films. © 2008 Institute of Food Science and Technology