Tosun, Metiner

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Profile URL
https://hdl.handle.net/20.500.14365/6740
Name Variants
Tosun, M.
Tosun, M
TOSUN, M
Job Title
Email Address
metiner.tosun@ieu.edu.tr
Main Affiliation
09.02. Internal Sciences
Status
Current Staff
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ORCID ID
0000-0002-2233-5720
Scopus Author ID
7003740001
Turkish CoHE Profile ID
76045C82A5CFC256
Google Scholar ID
HQ1-CF4AAAAJ
WoS Researcher ID
R-1615-2019
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CV MTosun_April 2026.pdf (182.69 KB)

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ZERO HUNGER2
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GOOD HEALTH AND WELL-BEING3
GOOD HEALTH AND WELL-BEING
8
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QUALITY EDUCATION4
QUALITY EDUCATION
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GENDER EQUALITY5
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CLEAN WATER AND SANITATION6
CLEAN WATER AND SANITATION
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AFFORDABLE AND CLEAN ENERGY7
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DECENT WORK AND ECONOMIC GROWTH8
DECENT WORK AND ECONOMIC GROWTH
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INDUSTRY, INNOVATION AND INFRASTRUCTURE9
INDUSTRY, INNOVATION AND INFRASTRUCTURE
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REDUCED INEQUALITIES10
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SUSTAINABLE CITIES AND COMMUNITIES11
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RESPONSIBLE CONSUMPTION AND PRODUCTION12
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PEACE, JUSTICE AND STRONG INSTITUTIONS16
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Documents

33

Citations

433

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Documents

34

Citations

422

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Scholarly Output

21

Articles

14

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147/358

Supervised MSc Theses

1

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WoS Citation Count

92

Scopus Citation Count

88

Patents

0

Projects

3

WoS Citations per Publication

4.38

Scopus Citations per Publication

4.19

Open Access Source

17

Supervised Theses

1

JournalCount
Acta Physıologıca1
Bmc Cancer1
Bratislava Medical Journal1
Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi1
Febs Journal1
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  • Thumbnail Image
    Article
    Citation - WoS: 18
    Citation - Scopus: 19
    Differential Expression of Store-Operated Calcium- and Proliferation-Related Genes in Hepatocellular Carcinoma Cells Following Trpc1 Ion Channel Silencing
    (Springer, 2016-07-22) Selli, Cigdem; Pearce, Dominic A.; Sims, Andrew H.; Tosun, Metiner
    TRPC1 and store-operated Ca2+ (SOC) entry have previously been associated with hepatocellular carcinoma cell proliferation. The aim of the study was to determine genes and processes associated with TRPC1 down-regulation and the resulting increase of SOC entry and decrease in hepatocellular carcinoma cell proliferation. For this purpose, transcriptome analysis was performed to determine differentially expressed genes in TRPC1-silenced Huh7 cells. SOC entry- and proliferation-related genes correlated with TRPC1 down-regulation were also examined. Changes in SOC entry and cell proliferation were monitored in the TRPC1-silenced and parental cells and found to be significantly increased and decreased, respectively, in TRPC1-silenced cells. A total of 71 genes were significantly differentially expressed (40 up- and 31 down-regulated), including four mitogen-activated protein kinase (MAPK) signalling-associated genes. STIM1 levels were significantly up-regulated and negatively correlated with TRPC1 levels. In addition, expression of two cell cycle regulation genes, CDK11A/11B and URGCP, was observed to decrease, whereas ERBB3 and FGFR4, pro-survival genes, increased significantly in TRPC1-silenced cells. In conclusion, these results suggest reciprocal alterations in TRPC1 and STIM1 levels and a role for STIM1 in the regulation of SOC entry in TRPC1-silenced Huh7 cells. In addition to TRPC1, STIM1 may participate in Huh7 cell proliferation by regulating SOC entry. Alterations in MAPK signalling genes may be involved in diminished cell proliferation in TRPC1-silenced Huh7 cells. Similarly, changes in cell cycle regulating genes in TRPC1-silenced cells indicate possible cell cycle arrest along with compensatory up-regulation of ERBB3 growth factor receptor-amongst others-to maintain hepatocellular carcinoma cell proliferation.
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    Article
    Citation - WoS: 4
    Citation - Scopus: 4
    Trpc1 Ion Channel Gene Regulates Store-Operated Calcium Entry and Proliferation in Human Aortic Smooth Muscle Cells
    (Tubitak Scientific & Technical Research Council Turkey, 2016) Erac, Yasemin; Selli, Cigdem; Tosun, Metiner
    This study investigates whether the reciprocal changes in transient receptor potential canonical (TRPC) 1 and TRPC6 expressions, which have previously been observed in aging rat aorta, are functional in store-operated calcium (SOC) entry and proliferation in human vascular smooth muscle cells. TRPC1 levels were modulated via silencing and overexpression vectors in human primary aortic smooth muscle cells. Following TRPC1 gene modulation, TRPC1 and TRPC6 expression levels were measured using quantitative real-time RT-PCR. In functional analyses, real-time changes in intracellular calcium levels and cell proliferation were determined. Microarray analysis was performed to identify genes associated with functional alterations following TRPC1 silencing. TRPC1 expression was significantly increased in TRPC1-overexpressing cells and inhibited in TRPC1-silenced cells, as expected. TRPC6 expression was significantly decreased in TRPC1-overexpressing cells but not affected by TRPC1 silencing. SOC entry was significantly enhanced in TRPC1-silenced cells but not altered by TRPC1-overexpression. Furthermore, cell proliferation was correlated with changes in TRPC1 expression. Microarray analysis revealed that cell cycle-associated genes were significantly differentially expressed in TRPC1-silenced cells. In addition, STIM1 levels were downregulated significantly following TRPC1 silencing. Data suggest that TRPC1 has a functional role in SOC entry regulation as well as in human aortic smooth muscle cell proliferation.
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    Article
    Citation - WoS: 6
    Citation - Scopus: 7
    Effects of Cell Seeding Density on Real-Time Monitoring of Anti-Proliferative Effects of Transient Gene Silencing
    (Bmc, 2016-12) Selli, Cigdem; Erac, Yasemin; Tosun, Metiner
    Background: Real-time cellular analysis systems enable impedance-based label-free and dynamic monitoring of various cellular events such as proliferation. In this study, we describe the effects of initial cell seeding density on the anti-proliferative effects of transient gene silencing monitored via real-time cellular analysis. We monitored the realtime changes in proliferation of Huh7 hepatocellular carcinoma and A7r5 vascular smooth muscle cells with different initial seeding densities following transient receptor potential canonical 1 (TRPC1) silencing using xCELLigence system. Huh7 and A7r5 cells were seeded on E-plate 96 at 10,000, 5000, 1250 and 5000, 2500 cells well(-1), respectively, following silencing vector transfection. The inhibitory effects of transient silencing on cell proliferation monitored every 30 min for 72 h. Results: TRPC1 silencing did not inhibit the proliferation rates of Huh7 cells at 10,000 cells well(-1) seeding density. However, a significant anti-proliferative effect was observed at 1250 cells well(-1) density at each time point throughout 72 h. Furthermore, significant inhibitory effects on A7r5 proliferation were observed at both 5000 and 2500 cells well(-1) for 72 h. Conclusions: Data suggest that the effects of transient silencing on cell proliferation differ depending on the initial cell seeding density. While high seeding densities mask the significant changes in proliferation, the inhibitory effects of silencing become apparent at lower seeding densities as the entry into log phase is delayed. Using the optimal initial seeding density is crucial when studying the effects of transient gene silencing. In addition, the results suggest that TRPC1 may contribute to proliferation and phenotypic switching of vascular smooth muscle cells.
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    Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Effects of Kynurenic Acid and Choline on Lipopolysaccharide-Induced Cyclooxygenase Pathway
    (Walter De Gruyter Gmbh, 2023-06-01) Barış, Elif; Şimşek, Oguzhan; Uysal Yoca, Özge; Demir, Ayşe Banu; Tosun, Metiner; Yoca, Ozge Uysal
    Objectives: Inflammation can be endogenously modulated by the cholinergic anti-inflammatory pathway via calcium (Ca2+)-permeable alpha-7 nicotinic acetylcholine receptor (a7nAChR) ion channel expressed in immune cells. a7nAChR agonist choline and tryptophan metabolite kynurenic acid (KYNA) produces immunomodulatory effects. This study aimed to determine the effects of the choline and KYNA on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 pathway.Methods: In vitro inflammation model was produced via LPS administration in macrophage cells. To determine the effective concentrations, choline and KYNA were applied with increasing concentrations and LPS-induced inflammatory parameters investigated. The involvement of nAChR mediated effects was investigated with the use of non-selective nAChR and selective a7nAChR antagonists. The effects of choline and KYNA on COX-2 enzyme, PGE(2), TNFa, NF-?B and intracellular Ca2+ levels were analyzed.Results: LPS-induced COX-2 expression, PGE(2) TNFa and NF-?B levels were decreased with choline treatment while intracellular calcium levels via a7nAChRs increased. KYNA also showed an anti-inflammatory effect on the same parameters. Additionally, KYNA administration increased the effectiveness of choline on these inflammatory mediators.Conclusions: Our data suggest a possible interaction between the kynurenine pathway and the cholinergic system on the modulation of LPS-induced inflammatory response in macrophages.
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    Article
    Citation - WoS: 8
    Effects of Cdp-Choline and Choline on Cox Pathway in Lps-Induced Inflammatory Response in Rats
    (Asian Network Scientific Information-Ansinet, 2021-02-15) Barış, Elif; Simsek, O.; Efe, H.; Oncu, S.; Gelal, A.; Hamurtekin, Emre; Tosun, M.; Arici, M. A.
    Background and Objective: Cytidine-5-diphosphate-choline (CDP-choline) and choline activate the cholinergic anti-inflammatory pathway in case of inflammation. This study investigated the role of CDP-choline and choline along with the contribution of the cyclooxygenase (COX) pathway on the lipopolysaccharide (LPS)-induced endotoxemia model in rats. Materials and Methods: Endotoxemia model was induced by LPS administration. CDP-choline or choline 5 min before and 6 hrs after LPS injection. The sepsis severity, body weight changes, survival rate were evaluated. Serum prostaglandins, Tumour Necrosis Factor (TNF)-alpha, total choline levels were measured. COX-2 mRNA expression and protein levels were analyzed. Spleen tissues were evaluated histomorphological. One-way analysis of variance analysis (ANOVA) or Kruskal Wallis tests was used for statistical analysis. Results: COX-2 expressions in liver and brain tissues, serum prostaglandin E-2, 6-keto prostaglandin F-1 alpha, Thromboxane A(2) and TNF alpha levels were increased 24 hrs after LPS administration. Administrations of CDP-choline or choline were decreased COX-2 expression in the liver. Serum prostaglandin levels were decreased in the CDP-choline-treated group, whereas, only prostaglandin E-2 level was decreased in the choline-treated group. Total choline levels in serum and brain were increased after CDP-choline or choline administration. Accordingly, serum TNF alpha levels and TNF alpha expression in the liver were decreased in CDP-choline and choline-treated groups. TNF alpha expression in the brain was decreased in the choline-treated group, whereas, increased in the CDP-choline-treated group. Conclusion: CDP-choline and choline decreased LPS-induced COX-2 enzyme expression and prostaglandin levels in the periphery by increasing serum and brain total choline levels in the LPS-induced endotoxemia model in rat.
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    Article
    Citation - Scopus: 1
    Effects of 1-(2 (trim) on Receptor-Independent And-Dependent Contractile Responses in Rat Aorta
    (Tubitak Scientific & Technical Research Council Turkey, 2016) Selli, Cigdem; Erac, Yasemin; Tosun, Metiner
    Background/aim: This study investigates whether 1-(2-trifluoromethylphenyl)-imidazole (TRIM), originally proposed as a nitric oxide synthase inhibitor and also suggested to be an inhibitor of store-operated calcium entry in mouse anococcygeal muscle, inhibits receptor-independent and -dependent responses in rat thoracic aorta. Materials and methods: Cyclopiazonic acid-and serotonin-induced vascular responses were investigated in aortic segments isolated from male Sprague Dawley rats using isolated tissue experiments. Changes in intracellular calcium levels were also monitored via front surface fluorescence measurements in fura-2-loaded embryonic rat vascular smooth muscle cell line A7r5. Results: TRIM inhibited serotonin-mediated vascular contractions without affecting cyclopiazonic acid-induced responses. In addition, TRIM caused a nonlinear rightward shift in the serotonin concentration-response curve, possibly via serotonin receptor modulation. Conclusion: TRIM may have an impact on investigation of tissue-specific receptor-independent and -dependent vascular responses. It may also be used as a lead compound in the development of selective serotonin receptor modulators.
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    Research Project
    Vazospazm Gelişiminde Kapasitatif Kalsiyum Girişinin Farmakolojik ve Moleküler Yaklaşımlarla Kontrolü
    (2007) Kosova, Büket; Tosun, Metiner; Selli, Çiğdem; Eraç, Yasemin
    [Abstract Not Available]
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    Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Liraglutide Modulates Cyclooxygenase and α7 Acetylcholine Receptors: in Vitro and in Silico Insights Into Its Anti-Inflammatory Role in LPS-Induced Inflammation in Raw 264.7 Macrophages
    (Springer, 2025-05-31) Baris, Elif; Portakal, Huseyin Saygin; Aslan, Arda; Karagonlar, Zeynep Firtina; Tosun, Metiner; Firtina Karagonlar, Zeynep
    Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is well-established for its metabolic benefits, including glycemic control and weight loss. Beyond these roles, it exhibits significant anti-inflammatory properties, though the mechanisms remain underexplored. This study investigates the anti-inflammatory effects of liraglutide in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Results demonstrate that increasing concentrations of liraglutide suppresses LPS-elevated prostaglandin E2 (PGE2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha, a stable prostacyclin metabolite) and thromboxane A2 (TXA2), similar to that observed with conventional anti-inflammatory agents, ibuprofen and celecoxib. Mechanistic exploration reveals that liraglutide's anti-inflammatory action is dually-modulated by cyclooxygenase (COX) and nicotinic acetylcholine receptor (nAChR) signaling. The application of non-selective, non-competitive nAChR antagonist or selective and potent alpha 7-nAChR antagonist, mecamylamine (MEC) and methyllycaconitine (MLA), respectively, highlights the involvement of cholinergic pathways in liraglutide's activity. Based on in silico molecular docking analyses, liraglutide exhibits favorable binding affinities to COX-1, COX-2, prostacyclin synthase (PGIS), and alpha 7nAChRs, supporting its potential multi-target anti-inflammatory effects. These findings suggest that the therapeutic potential of liraglutide may go beyond metabolic regulation and may be promising for conditions in which metabolic and inflammatory pathways converge, including inflammation and modulation of cholinergic signaling.
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    Article
    Implications of Possible Hbv-Driven Regulation of Gene Expression in Stem Cell-Like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line
    (Mdpi, 2022-12-14) Demir, Ayse Banu; Benvenuto, Domenico; Karacicek, Bilge; Erac, Yasemin; Spoto, Silvia; Angeletti, Silvia; Ciccozzi, Massimo; Tosun, Metiner
    Elevated levels of STIM1, an endoplasmic reticulum Ca2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca2+ homeostasis-associated genes in STIM1- or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers.
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    Article
    Citation - WoS: 23
    Citation - Scopus: 22
    Functional Consequences of Enhanced Expression of Stim1 and Orai1 in Huh-7 Hepatocellular Carcinoma Tumor-Initiating Cells
    (Bmc, 2019-07-31) Karacicek, B.; Erac, Y.; Tosun, Metiner
    BackgroundThe endoplasmic reticulum (ER) Ca2+ sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca2+ entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study investigated the functional consequences of enhanced expression of STIM1 and Orai1 in a tumor-initiating subpopulation of Huh-7hepatocellular carcinoma (HCC) cells that express epithelial cell adhesion molecule (EpCAM) and Prominin 1 (CD133).MethodsWe performed qRT-PCR, intracellular Ca2+ monitoring, protein analyses, and real-time cell proliferation assays on EpCAM(+)CD133(+) subpopulation of tumor-initiating Huh-7 HCC cells expressing high levels of STIM1 and/or Orai1. Statistical significance between the means of two groups was evaluated using unpaired Student's t-test.ResultsEnhanced STIM1 expression significantly increased ER Ca2+ release and proliferation rate of EpCAM(+)CD133(+) cells.ConclusionSTIM1 overexpression may facilitate cancer cell survival by increasing ER Ca2+-buffering capacity, which makes more Ca2+ available for the cytosolic events, on the other hand, possibly preventing Ca2+-dependent enzymatic activity in mitochondria whose Ca2+ uniporter requires much higher cytosolic Ca2+ levels.