PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 1Citation - Scopus: 1Lithium Treatment Rescues Dysfunctional Autophagy in the Cell Models of Tay-Sachs Disease(Academic Press Inc., 2024) Basirli,H.; Can,M.; Sengul,T.; Seyrantepe,V.Tay-Sachs disease is a rare lysosomal storage disorder (LSD) caused by a mutation in the HexA gene coding β-hexosaminidase A enzyme. The disruption of the HexA gene causes the accumulation of GM2 ganglioside resulting in progressive neurodegeneration in humans. Surprisingly, Hexa−/− mice did not show neurological phenotypes. Our group recently generated a murine model of Tay-Sachs disease exhibiting excessive GM2 accumulation and severe neuropathological abnormalities mimicking Tay-Sachs patients. Previously, we reported impaired autophagic flux in the brain of Hexa/-Neu3−/− mice. However, regulation of autophagic flux using inducers has not been clarified in Tay-Sachs disease cells. Here, we evaluated the effects of lithium treatment on dysfunctional autophagic flux using LC3 and p62 in the fibroblast and neuroglia of Hexa−/-Neu3−/− mice and Tay-Sachs patients. We discovered the clearance of accumulating autophagosomes, aggregate-prone metabolites, and GM2 ganglioside under lithium-induced conditions. Our data suggest that targeting autophagic flux with an autophagy inducer might be a rational therapeutic strategy for the treatment of Tay-Sachs disease. © 2024 Elsevier Inc.Article Citation - WoS: 6Citation - Scopus: 6Biomolecular Fingerprints of the Effect of Zoledronic Acid on Prostate Cancer Stem Cells: Comparison of 2d and 3d Cell Culture Models(Academic Press Inc., 2024) Güler,G.; Acikgoz,E.; Mukhtarova,G.; Oktem,G.Revealing the potential of candidate drugs against different cancer types without disrupting normal cells depends on the drug mode of action. In the current study, the drug response of prostate cancer stem cells (PCSCs) to zoledronic acid (ZOL) grown in two-dimensional (2D) and three-dimensional (3D) culture systems was compared using Fourier transform-infrared (FT-IR) spectroscopy which is a vibrational spectroscopic technique, supporting by biochemical assays and imaging techniques. Based on our data, in 2D cell culture conditions, the ZOL treatment of PCSCs isolated according to both C133 and CD44 cell surface properties induced early/late apoptosis and suppressed migration ability. The CD133 gene expression and protein levels were altered, depending on culture systems. CD133 expression was significantly reduced in 2D cells upon ZOL treatment. FT-IR data revealed that the integrity, fluidity, and ordering/disordering states of the cell membrane and nucleic acid content were altered in both 2D and 3D cells after ZOL treatment. Regular protein structures decrease in 2D cells while glycogen and protein contents increase in 3D cells, indicating a more pronounced cytotoxic effect of ZOL for 2D cells. Untreated 3D PCSCs exhibited an even different spectral profile associated with IR signals of lipids, proteins, nucleic acids, and glycogen in comparison to untreated 2D cells. Our study revealed significant differences in the drug response and cellular constituents between 2D and 3D cells. Exploring molecular targets and/or drug-action mechanisms is significant in cancer treatment approaches; thus, FT-IR spectroscopy can be successfully applied as a novel drug-screening method in clinical research. © 2024 Elsevier Inc.Article Citation - WoS: 26Citation - Scopus: 26Multi-Route - Multi-Pathway Exposure To Trihalomethanes and Associated Cumulative Health Risks With Response and Dose Addition(Academic Press Inc., 2019) Genişoğlu, Mesut; Ergi Kaytmaz, Ceyda; Sofuoğlu, Sait CemilCumulative health risk estimation for exposure to mixtures is a current issue, which would present a useful tool for environmental and public health management. Cumulative risks were estimated with response and dose addition methods for individual multi-route - multi-pathway exposure to trihalomethanes and associated carcinogenic toxic risks in Izmir, Turkey. Exposure levels were estimated for ingestion, dermal, and inhalation routes using measured tap water and bottled water THM concentrations. Drinking, showering, hand and dish washing were the considered pathways. THM concentrations in air during the showering were modeled with two-resistance theory using tap water concentration data. The estimated carcinogenic risk levels for ingestion route were in the range of safe (< 10(-6)) to low priority (< 10(-4)), for dermal route all were in the safe zone (< 10(-6)), and for inhalation route were in the range of safe to high priority (> 10(-4)) zones, indicating ingestion and inhalation routes were of similar significance ahead of dermal exposure. Cumulative carcinogenic risks of THM compounds were estimated using simple (response) addition and dose addition using cumulative relative potency factor (CRPF) methods. CRPF method estimated the risks at lower levels compared to the simple addition, which originated from the use two different risk factor values for the index chemical in the method. Cumulative chronic-toxic risks were also assessed, rendering below the threshold risk levels for all routes. This study showed that multi-route - multi-pathway exposure assessment and cumulative risk assessment should together be considered for better environmental and public health management.Article Citation - WoS: 41Citation - Scopus: 43Chloride or Sulfate? Consequences for Ozonation of Textile Wastewater(Academic Press Inc., 2019) Öktem, Yalçın Aşkın; Yüzer, Burak; Aydın, Muhammed Iberia; Ökten, Hatice Eser; Meriç, Süreyya; Selçuk, HüseyinOzonation of chloride-rich textile wastewater is a common pretreatment practice in order to increase biodegradability and therefore meet the discharge limits. This study is the first to investigate ozone-chloride/bromide interactions and formation of hazardous adsorbable organic halogens (AOX) in real textile wastewater. Initially effect of ozonation on chloride-rich real textile wastewater samples were investigated for adsorbable organic halogens (AOX) formation, biodegradability and toxicity. After 15 min of ozonation, maximum levels of chlorine/bromine generation (0.3 mg/l) and AOX formation (399 mg/l) were reached. OUR and SOUR levels both increased by approximately 58%. Daphnia magna toxicity peaked at 100% for 10 min ozonated sample. Considering adverse effects of ozonation on chloride-rich textile industry effluents, we proposed replacement of NaCl with Na2SO4. Comparative ozonation experiments were carried out for both chloride and sulfate containing synthetic dyeing wastewater samples. Results showed that use of sulfate in reactive dyeing increased biodegradability and decreased acute toxicity. Although sulfate is preferred over chloride for more effective dyeing performance, the switch has been hampered due to sodium sulfate's higher unit cost. However, consideration of indirect costs such as contributions to biodegradability, toxicity, water and salt recovery shall facilitate textile industry's switch from chloride to sulfate.Article Mrna Decay Analysis in Drosophila Melanogaster: Drug-Induced Changes in Glutathione S-Transferase D21 Mrna Stability(Academic Press Inc., 2008) Akgül, Bünyamin; Tu, Chen-Pei D.We have established an in vivo system to investigate mechanisms by which pentobarbital (PB), a psychoactive drug with a sedative effect, changes the rate of decay of gstD21 mRNA (encoding a Drosophila glutathione S-transferase). Here we describe methods for the use of hsp70 promoter-based transgenes and transgenic lines to determine mRNA half-lives by RNase protection assays in Drosophila. We are able to identify and map putative decay intermediates by cRT-PCR and DNA sequencing of the resulting clones. Our results indicate that the 3′-UTR of gstD21 mRNA is responsive to PB by regulating mRNA decay and that the cis-acting element(s) responsible for the PB-mediated stabilization resides in a 59 nucleotide sequence in the 3′-UTR of the gstD21 mRNA (Akgül and Tu, 2007).Article Citation - WoS: 19Citation - Scopus: 22Absence of Superoxide Dismutase Activity Causes Nuclear Dna Fragmentation During the Aging Process(Academic Press Inc., 2014) Muid, Khandaker Ashfaqul; Karakaya, Hüseyin Çaglar; Koç, AhmetSuperoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1Δ and sod2Δ strains. However, ccs1Δ mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1Δ, sod2Δ, and ccs1Δ mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.Article Citation - WoS: 8Citation - Scopus: 8Nkx3.1 Contributes To S Phase Entry and Regulates Dna Damage Response (ddr) in Prostate Cancer Cell Lines(Academic Press Inc., 2011) Erbaykent Tepedelen, Burcu; Özmen, Besra; Varışlı, Lokman; Gönen Korkmaz, Ceren; Debeleç Bütüner, Bilge; Hamid, Syed Muhammad; Çakmak, Özgür Yılmazer; Korkmaz, Kemal SamiNKX3.1 is an androgen-regulated homeobox gene that encodes a tissue-restricted transcription factor, which plays an important role in the differentiation of the prostate epithelium. Thus, the role of NKX3.1 as a functional topoisomerase I activity enhancer in cell cycle regulation and the DNA damage response (DDR) was explored in prostate cancer cell lines. As an early response to DNA damage following CPT-11 treatment, we found that there was an increase in the γH2AX (S139) foci number and that total phosphorylation levels were reduced in PC-3 cells following ectopic NKX3.1 expression as well as in LNCaP cells following androgen administration. Furthermore, upon drug treatment, the increase in ATM (S1981) phosphorylation was reduced in the presence of NKX3.1 expression, whereas DNA-PKcs expression was increased. Additionally, phosphorylation of CHK2 (T68) and NBS1 (S343) was abrogated by ectopic NKX3.1 expression, compared with the increasing levels in control PC-3 cells in a time-course experiment. Finally, NKX3.1 expression maintained a high cyclin D1 expression level regardless of drug treatment, while total γH2AX (S139) phosphorylation remained depleted in PC-3, as well as in LNCaP, cells. Thus, we suggest that androgen regulated NKX3.1 maintains an active DDR at the intra S progression and contributes to the chemotherapeutic resistance of prostate cancer cells to DNA damaging compounds.Article Citation - WoS: 119Citation - Scopus: 121Structure of Halothiobacillus Neapolitanus Carboxysomes by Cryo-Electron Tomography(Academic Press Inc., 2006) Schmid, Michael F.; Paredes, Angel M.; Khant, Htet A.; Soyer Dönmez, Ferda; Aldrich, Henry C.; Chiu, Wah; Shively, Jessup M.Carboxysomes are polyhedral bodies consisting of a proteinaceous shell filled with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO). They are found in the cytoplasm of all cyanobacteria and some chemoautotrophic bacteria. Previous studies of Halothiobacillus neapolitanus and Nitrobacter agilis carboxysomes suggest that the structures are either icosahedral or dodecahedral. To determine the protein shell structure more definitively, purified H. neapolitanus carboxysomes were re-examined by cryo-electron tomography and scanning transmission electron microscopy (STEM). Due to the limited tilt angles in the electron microscope, the tomographic reconstructions are distorted. Corrections were made in the 3D orientation searching and averaging of the computationally extracted carboxysomes to minimize the missing data effects. It was found that H. neapolitanus carboxysomes vary widely in size and mass as shown by cryo-electron tomography and STEM mass measurements, respectively. We have aligned and averaged carboxysomes in several size classes from the 3D tomographic reconstruction by methods that are not model-biased. The averages reveal icosahedral symmetry of the shell, but not of the density inside it, for all the size classes