Person: ELİBOL, BİRSEN
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Publication Open Access SIRT1 Gene Polymorphisms Affect the Protein Expression in Cardiovascular Diseases(2014-02-28) KILIC, Ulkan; GOK, Ozlem; Bacaksiz, AHMET; IZMIRLI, Muzeyyen; Elibol-Can, BİRSEN; Uysal, Omer; BACAKSIZ, AHMET; ELİBOL, BİRSEN; UYSAL, ÖMERCardiovascular disease (CVD), the leading cause of death worldwide, is related to gene-environment interactions due to epigenetic factors. SIRT1 protein and its downstream pathways are critical for both normal homeostasis and protection from CVD-induced defects. The aim of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A.G in the promoter region, rs7069102 C.G in intron 4 and rs2273773 C.T in exon 5 silent mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein expression as well as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in CVD patients as compared to controls. The frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were significantly higher in patients with CVD compared to control group. The risk for CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in carriers of mutant allele compared with carriers of wild-type allele pointing the protective role of C allele for both SNPs against CVD. For rs7895833, there was no significant difference in genotype and allele distributions between groups. SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as compared to control group. In contrast, level of eNOS protein was considerably low in the CVD patients. An increase in the SIRT1 expression in the CVD patients carrying mutant genotype for rs7069102 and heterozygote genotype for all three SNPs was observed. This is the first study reporting an association between SIRT1 gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS, TOS and OSIPublication Open Access Enhancement of Cisplatin sensitivity in human cervical cancer: epigallocatechin-3-gallate.(2015-01-26) KILIC, U; SAHIN, K; TUZCU, M; BASAK, N; KUCUK, O; ORHAN, C; Elibol-Can, BİRSEN; KILIC, ERDEM; SAHIN, F; ELİBOL, BİRSEN; KILIÇ, ERDEM; SU KÜÇÜK, ÖZLEMCisplatin is one of the effective chemotherapeutics in the treatment of several types of cancers. However, in addition to the efforts against to its toxicity, the amelioration of cisplatin sensitivity is an important point in treatment of cervical cancer. To do so, additional substances such as epigallocatechin gallate (EGCG), a polyphenol in green tea, have been used in combination with chemotherapeutics. We aimed to investigate the possible molecular pathways to potentiate cervical cancer cell (HeLa) growth inhibition by combination therapy of cisplatin and EGCG. HeLa cells were treated with EGCG (25µM), cisplatin (250 nM), and their combination for 24 h. Cell viability was determined by MTS Assay. We analyzed the expressions of NF-κB p65, COX-2, Nrf2, HO-1, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt byWestern blot analysis. Herein, we have demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of cervical cancer cells. EGCG improved efficacy of cisplatin treatment in HeLa cells by regulating NFκB p65, COX-2, p-Akt, and p-mTOR pathways, whereas it increased the expression levels of Nrf2/HO-1 in combined therapy. Our observations revealed that EGCG increases the sensitizPublication Open Access A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human(2015-03-18) Elibol-Can, BİRSEN; Kilic, Ulkan; Gok, Ozlem; DUNDAR, TOLGA TURAN; DUNDAROZ, Mehmet Rusen; Torun, EMEL; Erenberk, UFUK; Uysal, Omer; ERENBERK, UFUK; TORUN, EMEL; ELİBOL, BİRSEN; UYSAL, ÖMER; DÜNDAR, TOLGA TURANAging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.Publication Open Access Vitamin A deficiency induces structural and functional alterations in the molecular constituents of the rat hippocampus(2015-01-14) Elibol-Can, BİRSEN; Simsek-Ozek, Nihal; Severcan, Feride; Severcan, Mete; Jakubowska-Dogru, Ewa; ELİBOL, BİRSENTo date, no structural study has been carried out on the effects of vitamin A deficiency (VAD) on hippocampal macromolecules. Therefore, in the present study, the effect of dietary VAD on the structure, content and function of rat hippocampal molecules was investigated using Fourier transform IF spectroscopy. Male Wistar rats were randomly divided into three groups: an experimental group maintained on a vitamin A-deficient liquid diet (VAD, n 7); a control group maintained on a vitamin A-supplemented liquid diet (CON, n 9); a pure control group maintained on standard solid laboratory chow (PC, n 7). The PC group was included in the study to ensure that the usage of liquid diet did not influence the outcomes of VAD. Both the CON and PC groups were successfully discriminated from the VAD group by principal component analysis and hierarchical cluster analysis. The spectral analysis indicated a significant decrease in the contents of saturated and unsaturated lipids, cholesteryl esters. TAG and nucleic acids in the VAD group when compared with the CON group (P <= 0.05). In addition, a significant decrease in membrane fluidity and a significant increase in lipid order (e.g. acyl chain flexibility) were observed in the VAD group (P<0.001). The results of the artificial neural network analysis revealed a significant decrease in the alpha-helix structure content and a significant increase in the turn and random coil structure contents, indicating protein denaturation, in the VAD group when compared with the CON and PC groups (P <= 0.05). Dietary exclusion of vitamin A for 3 months apparently had an adverse impact on compositional, structural and dynamical parameters. These changes can be due to increased oxidative stress, confirming the antioxidant protection provided by vitamin A when used as a dietary supplement at low-to-moderate doses.