Browsing by Subject "Selenium"
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Item Open Access Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a selective survival mechanism?(American Association for Cancer Research, 2003) Irmak, M. B.; Ince, G.; Ozturk, M.; Cetin Atalay, R.Selenium is essential to human health, and its deficiency is associated with different diseases including liver necrosis. Selenium is protective against viral hepatitis and hepatocellular carcinoma (HCC). The underlying molecular mechanisms of selenium effects are not well known. In this study, in vitro response of HCC-derived cell lines to selenium deficiency is examined alone or in conjunction with Vitamin E and copper/zinc. Here, we show that itt vitro selenium deficiency in a subset of HCC-derived cell lines causes oxidative stress and cytochrome c release with subsequent cell death by apoptosis. The oxidative stress and consequent cell death induced by selenium deficiency on these cells are reverted by the antioxidant effect of Vitamin E. However, most HCC cell lines (10 of 13) tolerate selenium deficiency. Consequently, they escape apoptosis. Moreover, nine of these tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their genomes, and some display p53-249 mutation, indicating past exposure to HBV or aflatoxins, established factors for oxidative stress and cancer risk in liver. An HBV-transfected clone (2.2.15) of the sensitive HepG2 cell line has gained tolerance to selenium deficiency. Our findings indicate that selenium deficiency induces apoptosis in some "hepatocyte-like" cells. However, most HCC cells, particularly HBV-related ones, tolerate selenium deficiency and escape its deadly consequences. Thus, as demonstrated by the gain of survival capacity of apoptosis-sensitive cell lines with Vitamin E, such malignant cells have acquired a selective survival advantage that is prominent under selenium-deficient and oxidative-stress conditions.Item Open Access Characterization of programmed cell death induced by oxidative stress in selenium - deficient hepatocellular carcinoma cells(Bilkent University, 1999) İnce, GülayşeSelenium (Se) plays an important role in eliminating the reactive oxygen species generated during oxidative stress. Se-containing selenocysteine is an essential amino acid required for the synthesis of many selenoproteins, such as glutathione peroxidase. Se-dependent glutathione peroxidase is the major en2yme that metabolizes organic and hydrogen peroxides in the cell. It appears that Se manifests its antioxidant effect through the selenoproteins. Se deficiency causes a wide range of pathological conditions. Keshan disease, characterized by cardiomyocyte and liver cell death, defined as "necrosis", was found to be associated with Se deficiency. Se deficiency is also observed in liver cirrhosis, alcoholic liver disease, HIV positive and AIDS patients, thyroid hormone abnormalities, etc. Moreover, epidemiological studies show that Se deficiency increases the risk of many cancer types, including hepatocellular carcinoma (HCC). The molecular mechanisms of the pathologies associated with Se deficiency are mostly unknown. In this study, the in vitro responses of human hepatocellular carcinoma cells, to Se deficiency have been examined. Apoptotic changes (nuclear condensation, positive annexin V staining, genomic DNA breaks) are detected in Huh7, HepG2, and Mahlavu cells under Se-deficient culture conditions. Hydrogen peroxide addition into the culture medium aggravates apoptosis. Such changes are prevented by the supplementation of Se. The Se-dependent glutathione peroxidase enzyme is shown to be reduced in cells grown under Se-deficient conditions, explaining the build up of intracellular oxidative stress. It is proposed that the cell death observed in many pathologies associated with Se deficiency, is the result of the programmed cell death, triggered by an increase in intracellular oxidative stress, as opposed to necrotic cell death. Hep3B, Hep3B-TR, Hep40, PLC/PRF/5 and BC1/R14 cell lines have not displayed cell death when grown in Se-deficient conditions and were resistant to hydrogen peroxide, as well. The presence of such cell lines and the differential sensitivities manifested by HepG2, Huh7 and Mahlavu suggest a complete or partial gained resistance for apoptosis, which may contribute to the onset or progression of HCC, consistent with the increased risk of HCC in Se deficiency.Item Open Access Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium(Elsevier, 2010) Erkekoglu, P.; Rachidi, W.; Yuzugullu, O. G.; Giray, B.; Favier, A.; Ozturk, M.; Hincal, F.Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates' testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicular cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30. nM sodium selenite (SS), and 10 μM selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)-phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status. © 2010 Elsevier Inc.Item Open Access Induction of ROS, p53, p21 in DEHP-and MEHP-exposed LNCaP cells-protection by selenium compunds(Elsevier, 2011-07) Erkekoglu, P.; Rachidi, W.; Yazgullu, O. G.; Giray, B.; Ozturk, M.; Favier, A.; Hincal, F.This study was designed to investigate the hypothesis that the toxic effects of di(2-ethylhexyl)phthalate (DEHP), the most abundantly used plasticizer and ubiquitous environmental contaminant that cause alterations in endocrine and spermatogenic functions in animals is mediated through the induction of reactive oxygen species (ROS) and activation of nuclear p53 and p21 proteins in LNCaP human prostate adenocarcinoma cell line. Protective effects of two selenocompounds, sodium selenite (SS) and selenomethionine (SM) were also examined. It was demonstrated that 24. h exposure of the cells to 3. mM DEHP or its main metabolite, mono(2-ethylhexyl)phthalate (MEHP, 3 μM) caused strongly amplified production of ROS. Both SS (30. nM) and SM (10 μM) supplementations reduced ROS production, and p53 and p21 activation that induced significantly only by MEHP-exposure. The overall results of this study indicated that the induction of oxidative stress is one of the important mechanisms underlying the toxicity of DEHP and this is mainly through the effects of the metabolite, MEHP. Generated data also emphasized the critical role of Se in modulation of intracellular redox status, implicating the importance of the appropriate Se status in cellular response against testicular toxicity of phthalates. © 2011 Elsevier Ltd.Item Open Access Macroscopic photoconductive nanowire arrays(IEEE, 2011) Bayındır, Mehmet; Yaman, Mecit; Özgür, Erol; Aktaş, Ozan; Khudiyev, Tural; Kanık, Mehmet; Deniz, HakanA novel high-throughput fabrication technique to produce polymer embedded functional chalcogenide nanowire arrays is demonstrated. Indefinitely-long selenium nanowire arrays are obtained and their size dependent photoconductivity is investigated. Logarithmic increase in photo-conductance is observed. © 2011 IEEE.Item Open Access Na+/I-symporter and type 3 iodothyronine deiodinase gene expression in amniotic membrane and placenta and its relationship to maternal thyroid hormones(2013) Akturk, M.; Oruc, A.S.; Danisman, N.; Erkek, S.; Buyukkagnici, U.; Unlu, E.; Tazebay, U.H.Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus from the elevated maternal thyroid hormones. Na+/I- symporter (NIS) is a plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives were to establish the distribution of NIS and D3 gene expressions in the placenta and the amniotic membrane and to investigate the relationship between placental D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were studied with the total mRNA RT-PCR method in tissues from maternal placenta (n = 49), fetal placenta (n = 9), and amniotic membrane (n = 9). NIS and D3 gene expressions were shown in the fetal and maternal sides of the placenta and amniotic membrane. Mean blood selenium level was 66 ± 26.5 μg/l, and median UIC was 143 μg/l. We could not demonstrate any statistically significant relationship of spot UIC and blood selenium with NIS and D3 expression (p > 0.05). Positive correlations were found between NIS and thyroxine-binding globulin (TBG) (r = 0.3, p = 0.042) and between D3 and preoperative glucose levels (r = 0.4, p = 0.006). D3 and NIS genes are expressed in term placenta and amniotic membrane; thus, in addition to placenta, amniotic membrane contributes to regulation of maternofetal iodine and thyroid hormone transmission. Further studies are needed to clarify the relationship between maternal glucose levels and placental D3 expression and between TBG and placental NIS expression. © 2013 Springer Science+Business Media New York.Item Open Access SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer(National Academy of Sciences, 2009) Sayan, A. E.; Griffiths, T. R.; Pal, R.; Browne G. J.; Ruddick, A.; Yagci, T.; Edwards, R.; Mayer, N. J.; Qazi, H.; Goyal, S.; Fernandez, S.; Straatman, K.; Jones G. D. D.; Bowman, K. J.; Colquhoun, A.; Mellon, J. K.; Kriajevska, M.; Tulchinsky, E.The epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene and induce EMT in vitro. However, their relevance to human cancer is insufficiently studied. Here, we performed a comparative study of SIP1 and ZEB1 proteins in cancer cell lines and in one form of human malignancy, carcinoma of the bladder. Whereas ZEB1 protein was expressed in all E-cadherin-negative carcinoma cell lines, being in part responsible for the high motility of bladder cancer cells, SIP1 was hardly ever detectable in carcinoma cells in culture. However, SIP1 represented an independent factor of poor prognosis (P = 0.005) in a series of bladder cancer specimens obtained from patients treated with radiotherapy. In contrast, ZEB1 was rarely expressed in tumor tissues; and E-cadherin status did not correlate with the patients' survival. SIP1 protected cells from UV- and cisplatin-induced apoptosis in vitro but had no effect on the level of DNA damage. The anti-apoptotic effect of SIP1 was independent of either cell cycle arrest or loss of cell-cell adhesion and was associated with reduced phosphorylation of ATM/ATR targets in UV-treated cells. The prognostic value of SIP1 and its role in DNA damage response establish a link between genetic instability and metastasis and suggest a potential importance for this protein as a therapeutic target. In addition, we conclude that the nature of an EMT pathway rather than the deregulation of E-cadherin per se is critical for the progression of the disease and patients' survival.Item Open Access Transcriptome profiles associated with selenium-deficiency-dependent oxidative stress identify potential diagnostic and therapeutic targets in liver cancer cells(Scientific and Technical Research Council of Turkey - TUBITAK,Turkiye Bilimsel ve Teknik Arastirma Kurumu, 2021-04-20) Gözen, D.; Kahraman, D. C.; Narcı, K.; Shehwana, H.; Konu, Özlen; Çetin-Atalay, RengülHepatocellular carcinoma (HCC) is one of the most common cancer types with high mortality rates and displays increased resistance to various stress conditions such as oxidative stress. Conventional therapies have low efficacies due to resistance and off-target effects in HCC. Here we aimed to analyze oxidative stress-related gene expression profiles of HCC cells and identify genes that could be crucial for novel diagnostic and therapeutic strategies. To identify important genes that cause resistance to reactive oxygen species (ROS), a model of oxidative stress upon selenium (Se) deficiency was utilized. The results of transcriptome-wide gene expression data were analyzed in which the differentially expressed genes (DEGs) were identified between HCC cell lines that are either resistant or sensitive to Se-deficiency-dependent oxidative stress. These DEGs were further investigated for their importance in oxidative stress resistance by network analysis methods, and 27 genes were defined to have key roles; 16 of which were previously shown to have impact on liver cancer patient survival. These genes might have Se-deficiency-dependent roles in hepatocarcinogenesis and could be further exploited for their potentials as novel targets for diagnostic and therapeutic approaches.