Person:
ELİBOL, BİRSEN

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Kurumdan Ayrılmıştır

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Organizational Unit

Tıp Fakültesi

First Name

BİRSEN

Last Name

ELİBOL

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Now showing 1 - 10 of 13

Open Access
High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions.
(2018-10-15) Elibol, BİRSEN; KILIC, U; ELİBOL, BİRSEN
SIRT1 protein, a member of Silent Information Regulator 2 (Sir2) protein family, have gained considerable attention as epigenetic regulators for a great area in the human physiology. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, cardiovascular diseases, cancer and neurodegeneration. Here, we provide an overview of the association of the increasing level of SIRT1 protein for regulating some disease related conditions such as obesity, cardiovascular diseases and neurodegeneration. This review also provides a detailed molecular understanding of the interaction of the some basic molecules with increasing SIRT1 levels rather than reduction of the SIRT1 expression. In this context, the current approaches to enhancing the expression of SIRT1 points the importance of epigenetics in several age-related diseases to provide a healthy aging by developing novel therapies which can prevent or damp the progression of some diseases.
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, ÖMER
Cardiovascular 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 OSI
Open Access
Angiotensin IV improves spatial memory in streptozotocin-induced diabetic rats by reducing oxidative stress and altering BDNF levels
(2021-01-01T00:00:00Z) KILIÇ, AYSU; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; Bulut, Huri; MERAL, İSMAİL; Sahin, Gulderen; KILIÇ, AYSU; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; MERAL, İSMAİL
In this study, we investigated the protective effects of angiotensin IV (Mg IV) on cognitive function in streptozotocin (STZ)-induced diabetic rats. Male Wistar albino rats, were randomly divided into four groups; control (C), diabetes (Dia, 60 mg/kg, STZ, i.p.), Mg IV (5 mu g/kg, s.c.) and Dia+Ang W. The passive avoidance and Morris water maze (MWM) tests were used to evaluate learning and memory performance. Behavioral tests were carried out between 21 and 30 days after the initial Ang IV injection. Hippocampi were dissected and retained for biochemical and Western blot analysis. The Dia group exhibited the poorest behavioral results, while the Dia+Ang W group performed highest on the MWM task. Superoxide dismutase, glutathione peroxidase, and malondialdehyde levels increased significantly in the Dia group compared to Dia+Ang IV. Brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate levels were significantly elevated, while levels of GABA(A) significantly decreased, in the Dia+Ang IV group compared to the Dia group. These findings suggest that peripheral administration of Ang IV ameliorated spatial memory in diabetic rats by decreasing hippocampal oxidative stress and BDNF levels.
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, ÖZLEM
Cisplatin 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 sensitiz
Open Access
Prenatal ethanol intoxication and maternal intubation stress alter cell survival and apoptosis in the postnatal development of rat hippocampus.
(2019-01-01) Sahbaz, CD; Elibol, BİRSEN; Beker, M; Kilic, U; Jakubowska-Doğru, E; ELİBOL, BİRSEN; ŞAHBAZ, ÇIĞDEM DILEK
It is well known that the fetal ethanol exposure and prenatal stress may have adverse effects on brain development. Interestingly, some morphological and functional recovery from their teratogenic effects that take place during brain maturation. However, mechanisms that underlie this recovery are not fully elucidated. The aim of this study was to examine whether the postnatal attenuation of fetal alcohol - and maternal stress‑induced morphological and functional deficits correlates with compensatory changes in the expression/activation of the brain proteins involved in inflammation, cell survival and apoptosis. In this project, we investigated the hippocampus which belongs to the brain regions most susceptible to the adverse effects of prenatal ethanol exposure. Pregnant rat dams were administered ethanol (A) or isocaloric glucose solution (IC) by a gastric intubation during gestational days 7-20. The pure control group received ad libitum laboratory chow and water with no other treatment. The hippocampi of fetal-ethanol and control pups were examined at the postnatal day (PD)1, PD10, PD30 and PD60. Moderate fetal-ethanol exposure and prenatal intubation stress caused a significant increase in molecular factors relating to inflammation (iNOS) and cell survival/apoptosis pathways (PTEN, GSK-3 and ERK) at birth, with a rapid compensation from these developmental deficits upon removal of alcohol at PD10. Indeed, an increase in ERK1/2 and JNK1/2 activation at PD30 was observed with ethanol consumption. It indicates that the recovery process in A and IC brains started soon after the birth upon the ethanol and stressor withdrawal and continued until the adulthood.
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 TURAN
Aging 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.
Open Access
Prenatal exposure of diclofenac sodium alters the behavioral development of young Wistar rats.
(2019-10-14) Elibol, BİRSEN; Aritan, Oğur; Doğru, H; ELİBOL, BİRSEN
Diclofenac sodium (DS), a potent inhibitor of cyclooxygenase, reduces the release of arachidonic acid and formation of prostaglandins. Being a nonsteroid drug that shows antiinflammatory action, the possible side effects of fetal DS administration gain importance in public and medical applications. Herein, the effects of DS administration (1 mg/kg) during gestational days 5–20 were investigated on the performance of Wistar rat pups in a variety of behavioral tasks. Four-week-old pups were subjected to sensory motor tests, a plus maze, an open field, the Morris water maze, and a radial arm maze. Fetal DS disrupted some sensory motor performances, such as visual placing and climbing in both females and males. In the open field, DS females had a higher level of anxiety and male DS pups habituated to the environment slowly compared to controls. The DS pups showed slower rates of learning, whereas no substantial between-group differences were found in the performance of spatial memory compared to both controls. Furthermore, working memory was negatively affected by fetal DS. In conclusion, it was indicated that DS administration during pregnancy had slight behavioral impacts with a delay in learning and a defect in the short-term memory in juvenile rats.
Open Access
Chemopreventive efficacy of stampidine in a murine breast cancer model
(2020-02-07T00:00:00Z) Sahin, Kazim; Orhan, Cemal; Ozercan, Ibrahim Hanifi; Tuzcu, Mehmet; ELİBOL, BİRSEN; ŞAHİN, TAHA KORAY; Kilic, Ulkan; Qazi, Sanjive; Uckun, Fatih Mehmet; ELİBOL, BİRSEN
Background: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model. Methods: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks. Results: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2. Conclusion: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
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, BİRSEN
To 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.
Open Access
Effect of Restraint Stress on Plasma PTH Concentration and Its Molecular Targets Expressions in Wistar Rats
(2018-10-01) ELİBOL, BİRSEN; Terzioglu-Usak, Sule; Güler, Cansu; Dalli, Tugce; Aysan, Erhan; TERZİOĞLU, ŞULE; ELİBOL, BİRSEN
Background: There are limited numbers of experimental studies related to the potential role of parathormone/parathyroid hormone (PTH) in response to psychological stress. In the current study, we aimed to cross-examine, for the first time, changes in PTH plasma concentration and the expression of its molecular targets mediated by restraint stress in rats. Methods: Male Wistar rats (n = 42) were separated into control and stressed groups. They were further divided into two groups that received chronic restraint stress (CRS) for 7 and 28 consecutive days (n = 7 for each group). Elevated plus maze and tail suspension test were used to determine the anxiety- and depressive-like behaviors of a different set of rats including stress and control groups (n = 7 for each group). The plasma levels of adrenocorticotropic hormone (ACTH), corticosterone, and intact parathormone (iPTH) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, alterations in the expressions of glucocorticoid receptor (GR), calcium sensing receptor (CaSR), and parathormone receptor (PTHR1) of kidney and total thyroid gland tissues were estimated by Western Blotting. Results: There was no significant difference in the plasma level of iPTH while significant increases in the levels of ACTH and corticosterone were noted in the stressed-animals at day 7 and 21 (P = 0.010 and P = 0.016, respectively) of restraint stress. However, we found a negative correlation between iPTH and corticosterone levels in acute restraint stress (r = 0.771, P = 0.002). In addition, the expression of PTHR1 significantly decreased in the kidney at day 7 (P = 0.001) and in the thyroid gland at day 28 (P = 0.05) in response to CRS. Conclusions: To sum up, CRS has a significant effect on the expression of parathormone receptor rather than the iPTH concentration. The present results add a new dimension to stress research through the negative effect of chronic stress on the PTH signaling pathway.