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Üner, Göklem
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01. Izmir Institute of Technology
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Current Staff
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Sustainable Development Goals
1NO POVERTY
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2ZERO HUNGER
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3GOOD HEALTH AND WELL-BEING
4
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4QUALITY EDUCATION
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5GENDER EQUALITY
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6CLEAN WATER AND SANITATION
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7AFFORDABLE AND CLEAN ENERGY
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8DECENT WORK AND ECONOMIC GROWTH
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9INDUSTRY, INNOVATION AND INFRASTRUCTURE
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10REDUCED INEQUALITIES
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11SUSTAINABLE CITIES AND COMMUNITIES
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12RESPONSIBLE CONSUMPTION AND PRODUCTION
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13CLIMATE ACTION
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14LIFE BELOW WATER
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15LIFE ON LAND
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16PEACE, JUSTICE AND STRONG INSTITUTIONS
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17PARTNERSHIPS FOR THE GOALS
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Scholarly Output
13
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7
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41041/2076
Supervised MSc Theses
1
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1
WoS Citation Count
32
Scopus Citation Count
33
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WoS Citations per Publication
2.46
Scopus Citations per Publication
2.54
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5
Supervised Theses
2
| Journal | Count |
|---|---|
| Planta Medica | 4 |
| Scientific Reports | 3 |
| Chemical Research in Toxicology | 1 |
| Phytochemistry | 1 |
| Phytochemistry Reviews | 1 |
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13 results
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Now showing 1 - 10 of 13
Article Citation - WoS: 8Citation - Scopus: 9Neuroprotective Metabolites Via Fungal Biotransformation of a Novel Sapogenin, Cyclocephagenol(Nature Research, 2022) Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Üner, Göklem; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringCyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study were; (i) to perform microbial transformation studies on cyclocephagenol (1) using Astragalus endophyte, Alternaria eureka 1E1BL1, followed by isolation and structural characterization of the metabolites; (ii) to investigate neuroprotective activities of the metabolites; (iii) to understand structure–activity relationships towards neuroprotection. The microbial transformation of cyclocephagenol (1) using Alternaria eureka resulted in the production of twenty-one (2–22) previously undescribed metabolites. Oxidation, monooxygenation, dehydration, methyl migration, epoxidation, and ring expansion reactions were observed on the triterpenoid skeleton. Structures of the compounds were established by 1D-, 2D-NMR, and HR-MS analyses. The neuroprotective activities of metabolites and parent compound (1) were evaluated against H2O2-induced cell injury. The structure–activity relationship (SAR) was established, and the results revealed that 1 and several other metabolites had potent neuroprotective activity. Further studies revealed that selected compounds reduced the amount of ROS and preserved the integrity of the mitochondrial membrane. This is the first report of microbial transformation of cyclocephagenol.Article Citation - WoS: 4Citation - Scopus: 5Identification of a Noncanonical Necrotic Cell Death Triggered Via Enhanced Proteolysis by a Novel Sapogenol Derivative(American Chemical Society, 2020) Üner, Göklem; Bedir, Erdal; Tağ, Özgür; Üner, Göklem; Erzurumlu, Yalçın; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringSmall molecules which activate distinct cell death pathways have promising high potential for anticancer drug research. Especially, regulated necrosis draws attention as an alternative cell death mechanism to overcome the drug resistance. Here, we report that a new semisynthetic saponin analogue (AG-08) triggers necrotic cell death with unprecedented pathways. AG-08-mediated necrosis depends on enhanced global proteolysis involving calpains, cathepsins, and caspases. Moreover, AG-08 generates several alterations in lysosomal function and physiology including membrane permeabilization, redistribution toward the perinuclear area, and lastly excessive tubulation. As a consequence of lysosomal impairment, the autophagic process was abolished via AG-08 treatment. Collectively, in addition to its ability to induce necrotic cell death, which makes AG-08 a promising candidate to cope with drug resistance, its unique activity mechanisms including autophagy/lysosome impairment and enhancement of proteolysis leading a strong death capacity emphasizes its potential for anticancer drug research. ©Article Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities(ACG Publications, 2024) Dizmen,B.; Üner, Göklem; Küçüksolak, Melis; Dizmen, Berivan; Bedir, Erdal; Kırmızıbayrak,P.B.; Bedir,E.; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 03. Faculty of EngineeringEndophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.Conference Object Citation - WoS: 1Secondary Metabolites From Endophytic Fungus Penicilium Roseopurpureum and Investigation of Their Cytotoxic Activities(Georg Thieme Verlag, 2022) Dizmen, Berivan; Dizmen, Berivan; Üner, Göklem; Bedir, Erdal; Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Küçüksolak, Melis; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of Engineering[No Abstract Available]Conference Object Short Lecture Novel Neuroprotective Metabolites Produced Via Biotransformation of Cyclocephagenol by Alternaria Eureka 1e1bl1(Georg Thieme Verlag, 2022) Küçüksolak, Melis; Üner, Göklem; Üner, Göklem; Bedir, Erdal; Ballar Kırmızıbayrak, Petek; Küçüksolak, Melis; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringNeurodegeneration refers to the loss of structure/function of neurons leading to neurological diseases including Alzheimerʼs and Parkinsonʼs. The discovery of novel therapeutics against neurodegenerative diseases has been an area of intense research as neurodegenerative diseases are a huge burden on society and the economy [1]. Numerous studies reported that natural products have the potential to prevent and treat neurodegeneration. Among these studies, the neuroprotective activities of cycloartane-type saponins are noteworthy [2], [3]. In our preliminary studies, the neuroprotective activity of cyclocephagenol, an aglycone of cyclocephaloside I from Astragalus microcephalus [4], was screened for H2O2-induced injury in SH-SY5Y cells. Based on the promising bioactivity of cyclocephagenol, the aims of this study were: i) to perform microbial transformation studies on cyclocephagenol using Alternaria eureka followed by isolation and structural characterization of the metabolites; ii) to investigate neuroprotective activities of the metabolites; iii) to understand structure-activity relationships towards neuroprotection.Article Citation - WoS: 4Citation - Scopus: 3Is Telomerase a Hidden Player? Therapeutic Potential of Natural Telomerase Activators Against Age-Related Diseases(Springer, 2022) Kuru, Gülten; Üner, Göklem; Bedir, Erdal; Üner, Göklem; Kuru, Gülten; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringThere is a huge demand for novel treatment and/or prevention approaches for age-related diseases, which reduce life quality and one of the main reasons for death worldwide. Many age-related diseases were found to be associated with dysfunctional telomeres, which accelerate aging process due to the decrease in repair potential of tissues. An enzyme called telomerase is mainly responsible for keeping telomeres healthful. In the last two decades, the progress in the field, including in vitro studies, preclinical data, and human trials, demonstrated that telomerase and related genes might be powerful targets for the treatment of those diseases. Considering telomerase reactivation as a treatment strategy in age-related degenerative diseases, telomerase activators obtained from natural products stand out as promising agents. Although various research showed that those activators have protective/therapeutic activity against age-related diseases, the role of telomerase activation is often neglected in studies. In this context, we focused on the natural products as telomerase activator and their activities on age-related diseases, specifically neurodegenerative, cardiovascular, and osteodegenerative disorders, in which telomere dysfunction plays a causal role. Thus, this review aims to draw attention to the possibility of telomerase activation in therapy, in which some well-known natural products such as telomerase activators might play a role.Conference Object A New Semi-Synthetic Sapogenol Derivative Inducing Regulated Necrosis(Georg Thieme Verlag, 2019) Üner, Göklem; Bedir, Erdal; Ballar Kırmızıbayrak, Petek; Üner, Göklem; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringSince saponin’s antitumor potency is relatively weak, researchers focus on their semi-synthetic modification to obtain structures with higher potencies. With the same motivation, we prepared a cytotoxic sapogenol derivative (AG-08) from cycloastragenol. Our preliminary studies revealed that AG-08 induced primarily necrotic cell death along with autophagic inhibition. Furthermore, immunoblotting experiments demonstrated that AG-08 promoted cleavage of various proteins such as ATGs, p62, and PARP-1.Article Citation - WoS: 7Citation - Scopus: 7Novel Regulation Mechanism of Adrenal Cortisol and Dhea Biosynthesis Via the Endogen Erad Inhibitor Small Vcp-Interacting Protein(Nature Publishing Group, 2022) İlhan, Recep; Yılmaz, Sinem; Üner, Göklem; Atalay Sahar, Esra; Çaylı, Sevil; Erzurumlu, Yalçın; Gözen, Oğuz; Ballar Kırmızıbayrak, Petek; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 03. Faculty of EngineeringEndoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2α, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion.Conference Object Citation - WoS: 1Phytochemical Studies on Mastic Gum of Pistacia Lentiscus Var. Chia Collected From Karaburun Peninsula and Neuroprotective Activities of the Isolates(Georg Thieme Verlag, 2022) Demir, Mehmet; Üner, Göklem; Üner, Göklem; Demir, Mustafa Muammer; Mu, Kurt; Bedir, Erdal; Aygün, M.; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03.09. Department of Materials Science and Engineering; 03. Faculty of Engineering[No Abstract Available]Master Thesis Preparation of Some Semi-Synthetic Saponin Analogs and Investigation of Their Mechanism of Action on Necrotic Cell Death(Izmir Institute of Technology, 2019) Üner, Göklem; Bedir, Erdal; Üner, Göklem; Bedir, Erdal; Ballar, Petek; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringSince antitumor potency of saponins is relatively weak, researchers focus on semi-synthetic modification of saponins to obtain highly potent structures. With the same motivation, we prepared cytotoxic sapogenol (AG-08), from cycloastragenol. Our preliminary studies revealed that AG-08 was inducing necrotic cell death together with autophagic inhibition. Furthermore, immunoblotting experiments suggested that AG-08 promoted cleavage of various proteins. A continuation study was performed in this thesis with aims of: i) verifying previous studies; ii) identifying molecular mechanism of AG-08; iii) preparing further analogs of AG-08 and deduce structure activity relationships(SAR). Accordingly, necrotic cell death and autophagic inhibition via AG-08 was verified, and cytotoxicity of AG-08 on 13 cell lines was examined. Furthermore, inhibitors of calpain-1, general caspases, cathepsin B/L/S, and caspase-8 were found to partially alleviate cell death, whereas cathepsin D/E inhibitor were not able to do. Additionally, lysosomal impairment due to loss of acidic nature was demonstrated. Later data and effect of cathepsin inhibitor on AG-08 mediated cell death suggest lysosomal membrane permeabilization. In synthesis part, 15 AG-08 analogs were prepared, three of which were cytotoxic. Additionally, active analogs triggered similar cell death mechanism with AG-08. SAR evaluation reveals that presence of tosyl, and tetrahydrofuran ring are required for activity, while double bond at C-6 is not essential. Consequently, this thesis provides important data on mechanism of necrotic cell death and autophagic inhibition via AG-08 treatment as well as relationship between structure and activity. However, further studies are warranted to clarify complete mechanism of AG-08 and substantiate structure activity relationship deductions.