Tosun, Çiğdem
Loading...
Profile URL
Name Variants
Tosun, Cigdem
Tosun, C
Tosun, Ç
Tosun, Ç.
Tosun, C.
Tosun, C
Tosun, Ç
Tosun, Ç.
Tosun, C.
Job Title
Email Address
cigdemtosun@iyte.edu.tr
Main Affiliation
04.03. Department of Molecular Biology and Genetics
Status
Former Staff
Website
ORCID ID
Scopus Author ID
Turkish CoHE Profile ID
Google Scholar ID
WoS Researcher ID
Sustainable Development Goals
1NO POVERTY
0
Research Products
2ZERO HUNGER
1
Research Products
3GOOD HEALTH AND WELL-BEING
2
Research Products
4QUALITY EDUCATION
1
Research Products
5GENDER EQUALITY
0
Research Products
6CLEAN WATER AND SANITATION
1
Research Products
7AFFORDABLE AND CLEAN ENERGY
1
Research Products
8DECENT WORK AND ECONOMIC GROWTH
0
Research Products
9INDUSTRY, INNOVATION AND INFRASTRUCTURE
1
Research Products
10REDUCED INEQUALITIES
0
Research Products
11SUSTAINABLE CITIES AND COMMUNITIES
0
Research Products
12RESPONSIBLE CONSUMPTION AND PRODUCTION
1
Research Products
13CLIMATE ACTION
2
Research Products
14LIFE BELOW WATER
0
Research Products
15LIFE ON LAND
0
Research Products
16PEACE, JUSTICE AND STRONG INSTITUTIONS
0
Research Products
17PARTNERSHIPS FOR THE GOALS
0
Research Products
Documents
26
Citations
1278
h-index
15
Documents
30
Citations
1184
Scholarly Output
5
Articles
2
Views / Downloads
36115/2200
Supervised MSc Theses
3
Supervised PhD Theses
0
WoS Citation Count
112
Scopus Citation Count
115
Patents
0
Projects
1
WoS Citations per Publication
22.40
Scopus Citations per Publication
23.00
Open Access Source
5
Supervised Theses
3
| Journal | Count |
|---|---|
| Chemico - Biological Interactions | 1 |
| Journal of Neuropathology and Experimental Neurology | 1 |
Current Page: 1 / 1
Scopus Quartile Distribution
Competency Cloud
5 results
Scholarly Output Search Results
Now showing 1 - 5 of 5
Master Thesis Effects of Polyether Antibiotics on Autophagy(Izmir Institute of Technology, 2017) Khan, Nasar; Tosun, Çiğdem; Bedir, Erdal; Tosun, Çiğdem; Bedir, ErdalTreatment of cancer is one of the crucial enigma for scientific world and that’s why much effort needs to be put in place for the resolution of this challenge in alternative ways. Autophagy is believed to have an important role in tumor development and progression. The natural polyether antibiotics might be important chemotherapeutic agents to cure cancer by modulating autophagy. The primary goal of this study was to investigate the cytotoxic effects and autophagic mechanism of actions of three polyether antibiotics, one of which was a new secondary metabolite isolated from the marine Streptomyces cacaoi. The effects of these polyether antibiotics were investigated along with previously known autophagy modulators from the same group (Monensin). To achieve this goal, cytotoxicities of these polyether type compounds on three different type of cancer cell lines along with two healthy cell lines were investigated followed by a search to reveal the effects of these compounds on autophagy in cancer cell lines. Methodology of this study consists of mammalian cell culturing, cytotoxicity screening, staining and quantification of acidic compartments inside the cells and studying different autophagy markers along with other associated proteins under various conditions by using Western blotting. This study revealed that the tested polyether antibiotics were autophagy inhibitors as well as inducers of apoptosis in cervical, colorectal and prostate cancer cells. The obtained results will be of significance for the field of anticancer drugdevelopment; however, before one places these secondary metabolites as potential drug candidates, further studies including in vivo experiments are warranted.Master Thesis The Effect of Glibenclamide in Lipopolysaccharide Stimulated Brain Microvascular Endothelial Cells(Izmir Institute of Technology, 2019) Cihankaya, Hilal; Tosun, ÇiğdemEndothelial cells are essential components of the blood brain barrier (BBB) that regulate the exchange of solutes between the vasculature and the brain parenchyma. The integrity of the BBB is disrupted after central nervous system (CNS) injuries, and it has been associated with the Sur1-Trpm4 channels. Once these channels are opened, Na+ flows into the cells causing edema and cell death. To mimic CNS injuries in vitro, lipopolysaccharide (LPS) was used as an endotoxin to initiate proinflammatory mediators to increase endothelial permeability, and glibenclamide was used as an antagonist of Sur1-Trpm4 channels to reduce the inflammatory response and to maintain the structural integrity of BBB proteins. To demonstrate the role of glibenclamide following LPS stimulation, we determined the cytotoxicity of LPS in bEnd.3 cells by cleaved caspase-3 expression and propidium iodide staining. We also investigated the protective effect of glibenclamide on NF-B translocation, and BBB proteins; collagen IV (COL IV) and zonula occludens 1 (ZO-1) in LPS stimulated bEnd.3 cells. Our results revealed that 1g/ml LPS exposure was sufficient for NF-B nuclear translocation, along with a statistically significant decrease in the expressions of COL IV and ZO-1 proteins, and a significant increase in cell death. We also demonstrated that glibenclamide was able to restore the expressions of COL IV and ZO-1, significantly reduce NF-B translocation, and cell death. Taken together, LPS induction in bEnd.3 cells can be used to investigate endothelial cell dysfunction due to inflammation in stroke and trauma models and glibenclamide can be used as a protective drug to inhibit LPS stimulated inflammatory response, cell death and disruptions in the structures of key BBB proteins.Article Citation - WoS: 24Citation - Scopus: 23Polyethers Isolated From the Marine Actinobacterium Streptomyces Cacaoi Inhibit Autophagy and Induce Apoptosis in Cancer Cells(Elsevier, 2019) Khan, Nasar; Yılmaz, Sinem; Aksoy, Semiha; Uzel, Ataç; Tosun, Çiğdem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1-3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis.Master Thesis Investigation of the Pathology of Brain Derived Endothelial Cells in In-Vitro Hypoxia Models(01. Izmir Institute of Technology, 2021) Erdemli, Kısmet Tuğçe; Tosun, ÇiğdemThe blood brain barrier (BBB) is a vital structure that protects brain homeostasis. Endothelial cells (EC) have a significant role in regulating the BBB structure and function. Several studies have revealed the association of SUR1-TRPM4 channels that regulate this secondary damage of CNS injuries. After the activation of the channel, Na+ influx causes depolarization, cell swelling (edema) and ultimately oncotic cell death. Hypoxia inducing factor (HIF) transcription factor that has been reported to activate more than 100 genes to adapt to a hypoxic condition. Once Hif1-⍺ is translocated into the nucleus, it can dimerize with HIF1-ß to produce HIF that is critical in hypoxic conditions and regulate cell cycle arrest or cell death pathways. Hypoxia can occur in an O2 dependent and independent manner. In this study, CoCl2 and hypoxia chamber which was cost-effective and reliable were optimized. Cellular death was calculated with Trypan blue staining in this novel hypoxia chamber model and compared with CoCl2 models. In addition, morphological changes were observed in microscopic analysis. Hif1-⍺, caspase-3 and NF-κB translocation to the nucleus localization were quantified. Cell viability was different between the CoCl2 model and novel hypoxia chamber model at 24 hours. The cellular death increased with CoCl2 exposure, where no change was noted in the hypoxia chamber model. Time dependent Hif1-⍺ upregulation was also demonstrated that peaked at 12-hours. Finally, NF-κB translocation into the nucleus was significantly increased at 24 hours of hypoxia exposure. The results reveal that the inflatable hypoxia chamber model could be reliably used to mimic hypoxia in an in-vitro setting. Hif1-⍺ activated in a time dependent manner, along with NF-κB. The upregulation of these transcription factors can ultimately affect the cellular death mechanisms differentlyArticle Citation - WoS: 88Citation - Scopus: 92Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts(Oxford University Press, 2015) Mehta, Rupal I.; Tosun, Çiğdem; Ivanova, Svetlana; Tsymbalyuk, Natalia; Famakin, Bolanle M.; Kwon, Min Seong; Castellani, Rudy J.; Gerzanich, Volodymyr; Simard, J. MarcThe nonselective monovalent cation channel transient receptor potential melastatin 4 (Trpm4) is transcriptionally upregulated in neural and vascular cells in animal models of brain infarction. It associates with sulfonylurea receptor 1 (Sur1) to form Sur1-Trpm4 channels, which have critical roles in cytotoxic edema, cell death, blood-brain barrier breakdown, and vasogenic edema. We examined Trpm4 expression in postmortem brain specimens from 15 patients who died within the first 31 days of the onset of focal cerebral ischemia. We found increased Trpm4 protein expression in all cases using immunohistochemistry; transcriptional upregulation was confirmed using in situ hybridization of Trpm4 messenger RNA. Transient receptor potential melastatin 4 colocalized and coassociated with Sur1 within ischemic endothelial cells and neurons. Coexpression of Sur1 and Trpm4 in necrotic endothelial cells was also associated with vasogenic edema indicated by upregulated perivascular tumor necrosis factor, extravasation of serum immunoglobulin G, and associated inflammation. Upregulated Trpm4 protein was present up to 1 month after the onset of cerebral ischemia. In a rat model of middle cerebral artery occlusion stroke, pharmacologic channel blockade by glibenclamide, a selective inhibitor of sulfonylurea receptor, mitigated perivascular tumor necrosis factor labeling. Thus, upregulated Sur1-Trpm4 channels and associated blood-brain barrier disruption and cerebral edema suggest that pharmacologic targeting of this channel may represent a promising therapeutic strategy for the clinical management of patients with cerebral ischemia.