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Öğe Bioremediation Applications with Fungi(Springer International Publishing Ag, 2018) Saglam, Necdet; Yesilada, Ozfer; Saglam, Semran; Apohan, Elif; Sam, Mesut; Ilk, Sedef; Emul, Ezgi[Abstract Not Available]Öğe Biyoteknolojik işlemden geçmiş ve geçmemiş tekstil fabrikası boyalarının çeşitli organizmalar üzerine toksik etkisinin araştırılması(İnönü Üniversitesi, 2001) Apohan, ElifÖZET Yüksek Lisans Tezi BİYOTEKNOLOJİK İŞLEMDEN GEÇMİŞ VE GEÇMEMİŞ TEKSTİL FABRİKASI BOYALARININ ÇEŞİTLİ ORGANİZMALAR ÜZERİNE TOKSİK ETKİSİNİN ARAŞTIRILMASI ElifAPOHAN İnönü Üniversitesi Fen Bilimleri Enstitüsü Biyoloji Anabilim Dalı 51 +viii sayfa 2001 Danışman: Doç. Dr. Özfer YEŞİLADA Bileşiklerin pek çoğu toksik, genotoksik, mutajenik, teratojenik ve/veya karsinoj eniktir. Tekstil fabrikaları kullandıkları sentetik boyalardan dolayı renkli olan yüksek miktarda çıkış sularını deşarj etmektedir. Bu atık sular, çevrede organizmalar üzerine toksik etki gösterebilir. Bu çalışmada, tekstil boyalan olan Astrazon boyalarının çeşitli konsantrasyonlarının Funalia trogifmn misel çapı ve Escherichia coli, Pseudomonas aeruginosa, Streptococcus fecalis, Staphylococcus aureus gibi bakterilerin üreme yeteneği üzerine etkisi araştırılmıştır. Toksisite analizlerinde Astrazon boyalarının, fungus ve bakteri üzerine önemli oranda toksik olduğu bulunmuştur. Beyaz çürükçül funguslann boyaların rengini giderebildiği göz önüne alındığında, biyoteknolojik işlem sonrası Astrazon boyalarını detoksifiye edebileceği beklenebilir. Bu hipotezi test etmek amacıyla Astrazon boyalarının fungusla renginin giderimi araştırılmıştır. Funalia trogii test edilen bütün boyaların rengini gidermiştir. Bu boyaların biyoteknolojik işlem öncesi ve sonrası üremeyi indirgeyici etkisi test edilmiştir. Astrazon boyalan Funalia trogii ile biyoteknolojik işlemden geçirildiğinde rengi giderilmiş ve fungus ve bakteri üzerine toksik etkisi de önemli oranda azalmıştır. Toksik etkideki bu azalış hem Çevre Biyoteknolojisi açısından hem de rekalsitrant atık antılmasında önemlidir. ANAHTAR KELİMELER: Boya, beyaz çürükçül funguslar, toksik etki, re; bakteri, Funalia trogiiÖğe Cytotoxic and antimicrobial potential of benzimidazole derivatives(Wiley-V C H Verlag Gmbh, 2021) Kucukbay, Hasan; Uckun, Mustafa; Apohan, Elif; Yesilada, OzferNew benzimidazole derivatives were synthesized and their structures were characterized by spectroscopic and microanalysis techniques. The cytotoxic properties of ten benzimidazole derivatives, five of which were synthesized in our previous studies, were determined against the lung cancer cell line, A549, and the healthy lung epithelial cell line, BEAS-2B. Among the ten compounds tested, based on the 72-h incubation results, compound 12 was the most cytotoxic against the A549 cell line, whereas against the BEAS-2B cell line, it was as cytotoxic as cisplatin. The IC50 values of compound 12 were 3.98 and 2.94 mu g/ml for A549 and BEAS-2B cells, respectively. The cisplatin values were 6.75 and 2.75 mu g/ml for A549 and BEAS-2B cells, respectively. Compounds 10, 8, 7, and 13 showed toxic effects against A549 cells, but were less toxic against BEAS-2B cells than cisplatin. The antimicrobial activity of these compounds against pathogenic bacteria and yeasts was also evaluated based on their minimum inhibitory concentration (MIC) values. The compounds, except 12 and 13, generally showed higher antimicrobial activity against yeasts, compared with bacteria. Compound 12 showed better activity against Pseudomonas aeruginosa and Staphylococcus aureus than against Escherichia coli. Compounds 7, 8, and 11 were the most effective ones against the microorganisms, and yeasts were highly sensitive to these compounds with MIC values of 25-100 mu g/ml.Öğe ENDOGENOUS POLYAMINE CONTENT IN THE WHITE ROT FUNGI Coriolus (Trametes) versicolor AND Funalia trogii(Parlar Scientific Publications (P S P), 2010) Mutlu, Fatma; Apohan, Elif; Kahraman, SibelIn this study, changes in the content of polyamines (PAs) of the white rot fungi Coriolus (Trametes) versicolor ATCC 200801 and Funalia trogii ATCC 200800 were investigated. The effects of various parameters such as initial pH, temperature, time period and the agitation rate were studied and the optimal experimental conditions were decided. Spermidine (Spd) was the most abundant polyamine in two white rot fungi. The highest Spd content was obtained at 30 degrees C temperature, 150 rev/min agitation rate and pH 3.0 for C. versicolor for 6 day incubation period. Whereas, the highest Spd content for F. trogii was found at 40 degrees C temperature, 50 rev/min agitation rate and pH 5.0 in 6 day incubation period. As a conclusion, our data show that white rot fungi produce spermidine at determining optimal culture conditions. Moreover our results demonstrate that it is possible to increase the endogenous Spd content by selecting the most optimal conditions.Öğe ENHANCEMENT OF LACCASE PRODUCTION OF PRE-GROWN FUNGAL PELLETS IN WASTEWATER OF OLIVE OIL MILLS(Parlar Scientific Publications (P S P), 2011) Apohan, Elif; Yesilada, OzferPrevious works reported laccase production ability of batch cultures of white rot fungi in olive oil mill wastewater media (OOMW). Therefore, here, laccase production ability of repeated-batch cultures of Funalia trogii and Trametes versicolor pre-grown pellets in olive oil mill wastewater media (OOMW) was investigated and conditions for laccase production were optimized. The results indicated that high amounts of laccase could be obtained by using the best production conditions such as agitation, initial pellet amounts, initial pH, OOMW concentration and temperature. All these conditions were found to be important for laccase production. After optimization, the effect of various supplementary sources and inducer (glucose, malt extract, cheese whey and copper) on laccase production ability of these fungi and longevity of this production ability were examined in repeated-batch process. Presence of glucose, malt extract, cheese whey and copper positively affected the laccase production ability and longevity of the production. The fungal pellets also partially bioremediated the OOMW during laccase production and F. trogii pellets removed 33 % COD from OOMW effluent whilst T. versicolor removed 28 % in the first use.Öğe The evaluation of pre-grown mycelial pellets in decolorization of textile dyes during repeated batch process(Springer, 2010) Yesilada, Ozfer; Yildirim, Seval Cing; Birhanli, Emre; Apohan, Elif; Asma, Dilek; Kuru, FilizThis study was undertaken for the possibility of application of pre-grown pellets for biotechnological treatment of dyes and textile industry waste waters. Mycelial pellets of five different white rot fungi were tested for their dye decolorization activity. The pellets of Funalia trogii, Phanerochaete chrysosporium and Trametes versicolor were determined as the most effective ones. The decolorization ability of viable pellets was compared with the decolorization (adsorption) ability of dead pellets during repeated batch studies. Astrazon Black dye was decolorized effectively, about 90%, by viable pellets of all fungi during the first use. Viable F. trogii pellets were found as the most effective pellets. Upon pellet treatment not only a high decolorization but also reduced toxicity (antimicrobial activity) of the Astrazon Black dye was recorded. This type of decolorization activity with commercial or crude laccase was partially observed. Growing cells of F. trogii in batch system showed lower efficiency in color removal of mixed dyes compared to the pre-grown pellets in repeated batch system. The results in this study showed that mycelial pellets could effectively be used as an alternative to traditional physicochemical processes.Öğe Laccase production and dye decolorization by Trametes versicolor: application of Taguchi and Box-Behnken Methodologies(Turkish Biochem Soc, 2014) Gedikli, Serap; Aytar, Pinar; Buruk, Yeliz; Apohan, Elif; Cabuk, Ahmet; Yesilada, Ozfer; Burnak, NimetullahObjective: The aim of this study was to investigate the laccase production of Trametes versicolor under submerged fermentation condition. Then, dye decolorization by laccase was optimized using Box-Behnken methodology. Methods: The optimal culture conditions for producing high amount of laccase were determined using Taguchi methodology. The experiments were designed with five factors (glucose, yeast extract, CuSO4, inoculum size and pH) at three levels with orthogonal array layout of L27 (3(5)). Then, the optimum conditions for high decolorization activity of Reactive Blue 49 by obtained crude laccase were also investigated using Box-Behnken methodology. Results: The optimum culture conditions for production of high amounts of laccase were detected as 2 g L-1 of glucose, 5 g L-1 of yeast extract, 2mM of CuSO4, 4% of inoculum amount and pH 5.5. Yeast extract was the most effective factor, followed by CuSO4, inoculum, glucose and pH. Under these conditions, predicted values were in a good agreement with the actual experimental one. The predicted results showed that the maximum of Reactive Blue 49 decolorization as 98% could be obtained under the optimum conditions of pH 2.95, initial dye concentration 55.6 mg L-1, enzyme amount 0.76 mL and reaction time 46.91 min. The validity and practicability of this statistical optimization strategy was confirmed with the relation between predicted and experimental values. Conclusion: The results suggested that Taguchi method can be used in the optimization of laccase production process. Production of laccase by Trametes versicolor 2008001 can be effectively used for enzymatic decolorization according to the results of decolorization experiments in optimal levels.Öğe Moringa oleifera leaves: could solvent and extraction method affect phenolic composition and bioactivities?(Taylor & Francis Inc, 2021) Bennour, Naima; Mighri, Hedi; Bouhamda, Talel; Mabrouk, Mahmoud; Apohan, Elif; Yesilada, Ozfer; Kucukbay, HasanThis study was carried out to evaluate the effect of extraction methods (direct maceration (DM) and successive maceration (SM)) and solvents (dichloromethane (DCM), ethyl acetate (EAc), butanol (But), and aqueous extraction (Aqu)) on the phenolic composition and biological activities of Moringa oleifera leaves cultivated for the first time in Tunisia. Total polyphenol content (TPC), total flavonoid content (TFC) and LC-MS analysis were performed for all extracts. Antioxidant potential by DPPH, metal chelating, and FRAP assays, antibacterial activity against Staphylococcus aureus (ATCC 29213) and Escherichia coli (ATCC 25922) by the minimum inhibitory concentration method (MIC) and cytotoxic properties against lung cancer cells (A549), were determined. Phenolic compounds and biological activities of M. oleifera leaves depend on the method and the solvent used for the extraction of these bioactive substances. The But extract prepared by SM method exhibited the highest amounts of TPC (103.06 +/- 0.5 mg GAE/g DE) and showed the strongest potential antioxidant (CI50 = 0.26 mg/mL on DPPH test), antibacterial (MIC = 250 mu g/mL) and cytotoxic activities (GI(50) = 69.9 mu g/mL). LC-MS analysis showed that 28 phenolic compounds of 33 tested standards were found in M. oleifera leaves. The But extract obtained by SM method exhibited the highest amounts of rutin, quercetin and syringic acid.Öğe Polyamine and Laccase Production under Cadmium Stress in Trametes (Coriolus) versicolor and Funalia trogii(Ekoloji, 2014) Mutlu, Fatma; Kahraman, Sibel; Apohan, ElifÖz: Bu çalışmada, artan konsantrasyondaki kadmiyum (Cd) (0.1-200 mg/L) uygulamasının, ağır metalcevabında indikatör olan serbest poliaminlerin düzeyine ve lakkaz aktivitelerine olan etkisi beyaz çürükçülfunguslardan Trametes (Coriolus) versicolor and Funalia trogii ' de 6. ve 15. günlerde araştırıldı.Spermidin (Spd) her iki beyaz çürükçül fungusta da en yoğun bulunurken, Spermin (Spm) ve Putresin(Put) sadece eser düzeyde bulundu ya da belirlenemedi. En yüksek Spd düzeyi (1952.05 ?g/DW; 2391.54?g/DW) 1 ppm Cd uygulanan 15 günlük inkübasyon süresindeki sırasıyla T. versicolor and F. trogii ' de tespitedildi. Her iki türdeki lakkaz aktivitesi özellikle 15 günlük kültürlerde kendi kontrollarına göre önemlidüzeyde artış gösterdi. Lakkaz aktivitesinde en yüksek artış, 100 ppm Cd uygulanan 15 günlük T. versicolorkültürlerinde kontrol grubuna göre 19 kat daha yüksek bulunarak elde edildi. Kuru ağırlık 0.1 ve 1 ppm Cduygulanan 6 ve 15 günlük T. versicolor kültürlerinde belirgin bir artış göstermiştir. 6 ve 15 günlük F. trogiikültürlerinde bütün uygulama gruplarında elde edilen kuru ağırlık kontrol grubu ile kıyaslandığındabelirgin bir artışa neden olmuştur. Bu çalışma sonucu, kadmiyum uygulanan T. versicolor ve F. trogii kültürlerinde serbest Spd düzeyi ve lakkazaktivitesinde artış olduğunu gösterdi. Cd stresi altındaki T. versicolor ve F. trogii 'de serbest Spd düzeyi velakkaz aktivitesindeki artış ağır metal stresi ile mücadelede rol oynadığı fikrini verdi. Başlık (İngilizce): Kadmiyum Stresi Altındaki Trametes (Coriolus) versicolor ve Funalia trogii 'de Poliamin ve Lakkaz Üretimi Öz (İngilizce): In the present study the effect of increasing the concentrations of the heavy metal cadmium (Cd) (0.1-200ppm) on the free polyamines (PAs) level and laccase activity was studied in the white rot fungi Trametes(Coriolus) versicolor and Funalia trogii at 6 and 15 days. Spermidine (Spd) was the most abundant PA in the two white rot fungi, while Spermine (Spm), andPutrescine (Put) were found only in trace amounts or were not determined. The highest Spd levels(1952.05 ?g/DW and 2391.54 ?g/DW) were observed in 1 ppm Cd at 15 days of incubation in T. versicolorand F. trogii respectively. The laccase activity of both species, especially in the 15-day cultures, showed asignificant increase compared to the control. The highest increase was evident at 100 ppm Cd where thelaccase activity was over 19 fold higher than that of the control sample in the 15 day culture of T. versicolor.The dry biomass in the 0.1 and 1 ppm Cd concentrations showed a significant increase in T. versicolor in thesix and 15 day incubation periods. In all cases, the dry biomass in both the six and 15 day cultures of F. trogiishowed a significant increase compared to the control cultures.The findings gathered through this study show that Cd can amplify free Spd levels and increase laccaseactivity in T. versicolor and F. trogii. This increase under Cd stress suggests their possible role in combatingthe adverse effect of heavy metalÖğe Polyamine and Laccase Production under Cadmium Stress in Trametes (Coriolus) versicolor and Funalia trogii(Foundation Environmental Protection & Research-Fepr, 2014) Mutlu, Fatma; Kahraman, Sibel; Apohan, ElifIn the present study the effect of increasing the concentrations of the heavy metal cadmium (Cd) (0.1-200 ppm) on the free polyamines (PAs) level and laccase activity was studied in the white rot fungi Trametes (Coriolus) versicolor and Funalia trogii at 6 and 15 days. Spermidine (Spd) was the most abundant PA in the two white rot fungi, while Spermine (Spm), and Putrescine (Put) were found only in trace amounts or were not determined. The highest Spd levels (1952.05 mu g/DW and 2391.54 mu g/DW) were observed in 1 ppm Cd at 15 days of incubation in T versicolor and F. trogii respectively. The laccase activity of both species, especially in the 15-day cultures, showed a significant increase compared to the control. The highest increase was evident at 100 ppm Cd where the laccase activity was over 19 fold higher than that of the control sample in the 15 day culture of T versicolor. The dry biomass in the 0.1 and 1 ppm Cd concentrations showed a significant increase in T versicolor in the six and 15 day incubation periods. In all cases, the dry biomass in both the six and 15 day cultures of F. trogii showed a significant increase compared to the control cultures. The findings gathered through this study show that Cd can amplify free Spd levels and increase laccase activity in T versicolor and F. trogii. This increase under Cd stress suggests their possible role in combating the adverse effect of heavy metal stress.Öğe PRODUCTION OF LACCASE IN OLIVE OIL MILL WASTEWATER AND VINASSE BY IMMOBILIZED TRAMETES VERSICOLOR AND TRAMETES TROGII WITH DIFFERENT SUPPORTS(Parlar Scientific Publications (P S P), 2017) Apohan, Elif; Yesilada, OzferLaccase production ability of immobilized forms of Trametes trogii and Trametes versicolor in vinasse and olive oil mill wastewater (OOMW) was investigated. Immobilized fungi could be used repeatedly and successfully produced laccase enzyme under repeated-batch mode. While the highest laccase activity of T. trogii immobilized into alginate beads was 2.53 U/mL in vinasse after eleven cycles, the highest activity as 3.33 U/mL was obtained in OOMW after two cycles. The highest activities for T. trogii immobilized on pine cone particles (PCP) were 1.02 U/mL in vinasse and 3.02 U/mL in OOMW after five cycles and six cycles, respectively. On the other hand, the highest activity by T. versicolor immobilized into alginate beads was 1.28 U/mL in vinasse after fifteen cycles and 3.89 U/mL after two cycles in OOMW. For the fungus immobilized on PCP, the highest activities were 2.41 U/ml after two cycles and 3.29 U/mL after three cycles in vinasse and OOMW, respectively. Laccase production potential of the immobilized fungi in OOMW was higher than the forms in vinasse. The highest laccase activities obtained with the immobilized fungi were generally higher than the activities obtained by free cells Immobilized fungi also reduced the COD of these wastewaters.Öğe Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest(Taylor & Francis Ltd, 2013) Gokbulut, Aysun Adan; Apohan, Elif; Baran, YusufChronic lymphocytic leukemia (CLL), defined by accumulation of pathogenic B cells, has a very complex biology due to various factors such as inherited, host, and enviromental factors. Recently, finding new therapeutic agents or development of novel treatment strategies have been paid attention. Resveratrol and quercetin, important phytoalexins found in many plants, have been reported to have cytotoxic effects on various types of cancer. In this study, we examined cytotoxic, cytostatic, and apoptotic effects of these two important phenolic compounds on 232B4 human CLL cells. Cytotoxic effects of resveratrol and quercetin were determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using caspase-3 colorimetric assay. Annexin V-FITC/PI double staining was performed to measure apoptotic cell population. Effects of resveratrol and quercetin on cell cycle profiles of CLL cells were investigated by flow cytometry. Treatment of CLL cells with resveratrol and quercetin caused dose dependent inhibition of cell proliferation and increased apoptotic cell population through induction of caspase-3 activity. Cell cycle analysis displayed cell cycle arrest mainly in G0/G1 for both polyphenols. Our data, in total, showed for the first time that resveratrol and quercetin might block CLL growth through inducing apoptosis and cell cycle arrest.Öğe Synthesis a group of 5(6)-substituted benzimidazole Zn(II) and Co(II) complexes and investigation their cytotoxic and antimicrobial activities(Wiley, 2022) Yilmaz, Ulku; Apohan, Elif; Kucukbay, Hasan; Yilmaz, Ozgur; Tatlici, Eray; Yesilada, OzferA series of 5(6)-substituted benzimidazole ligand-zinc(II) and cobalt(II) complexes were synthesized and characterized by H-1, C-13 NMR, IR, CHN analysis techniques. In vitro, anticancer and antimicrobial activities of ligand and complexes were evaluated. The cytotoxic activities of compounds were investigated against the human lung adenocarcinoma (A549) cell lines and healthy human lung bronchial epithelium (BEAS2B) cells. Compounds 1, 6, and 8 were observed to exhibit higher cytotoxic activity than the others at the 72nd hour. Also, the compounds showed varying degrees of antimicrobial activity against the microorganisms used. Compounds 1, 5, and 8 were most effective against standard strains Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213. As for the antifungal activity, compounds 1, 5, 6, and 8 showed high antifungal activity against the yeast type fungi Candida albicans ATCC 90028 and Candida tropicalis.Öğe Synthesis and Evaluation of Novel Benzimidazole Conjugates Incorporating Amino Acids and Dipeptide Moieties(Bentham Science Publ Ltd, 2017) Bugday, Nesrin; Kucukbay, F. Zehra; Apohan, Elif; Kucukbay, Hasan; Serindag, Ayfer; Yesilada, OzferBackground: Amino acids, short peptide sequences and benzimidazole derivatives play an increasingly important role as therapeutics in areas including antibacterial, antifungal, antiviral, anti-inflammatory, antiparasitic, antibiofilm, antidiabetic, and anticancer. Methods: Some novel amino acids and glycine-glycine dipeptide benzimidazole conjugates were synthesized by facile acylation reactions through DCC mediated reactions and their structures were identified by H-1-NMR, C-13-NMR and FT-IR spectroscopic techniques and elemental analysis. In vitro antimicrobial activities of some compounds against Gram positive (Staphylococcus aureus and Enterobacter faceium NJ-1) and Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeasts (Candida albicans and Candida tropicalis) were determined by MIC method. Their antioxidant activities were also detected by DPPH method. Results: Sixteen novel benzimidazole conjugates incorporating glycine, alanine, phenylalanine, cysteine and glycine-glycine dipeptide were synthesized and their structures were identified by spectroscopic techniques and elemental analysis. All of the compounds tested showed in vitro antimicrobial and antioxidant activities. Conclusion: Sixteen novel benzimidazole amino acid/dipeptide conjugates were synthesized using DCC mediated one step reaction in moderate yield and high purity, under mild reaction conditions, with full retention of the original chirality. Amino acid or dipeptide substitutions at position 1 of the benzimidazoles were synthesized first time in this work. The results have indicated that the newly synthesized compounds possess low to moderate antimicrobial and antioxidant activities.Öğe Synthesis, cytotoxic and antimicrobial activities of novel cobalt and zinc complexes of benzimidazole derivatives(Elsevier Science Sa, 2017) Apohan, Elif; Yilmaz, Ulku; Yilmaz, Ozgur; Serindag, Ayfer; Kucukbay, Hasan; Yesilada, Ozfer; Baran, YusufIn this study fourteen novel cobalt (II) or zinc (II) complexes of benzimidazoles were synthesized from the 1-(4-substitutedbenzyl)-1H-benzimidazoles and CoCl2.6H(2)O or ZnCl2. Cytotoxic activities of novel complexes were investigated against lung cancer cells (A549) and BEAS-2B. Three of the examined compounds (1, 4 and 5) showed high cytotoxic activity against A549. While the IC50 of the cisplatin was 2.56 pg/mL for A549 cells at 72 h, the IC50 values of compounds 1, 4 and 5 were 1.97, 1.87 and 1.9 mu g/mL, respectively. IC50 values of these compounds for BEAS-2B cells were higher than the IC50 values for A549. While the IC50 values for BEAS-2B cells were 59.8, 24.5 and 32.67 mu g/mL, respectively, the IC50 of the cisplatin was determined as 2.53 pgimL in the present work. Three of the compounds have also high antimicrobial activity against all the microorganisms used. (C) 2016 Elsevier B.V. All rights reserved.Öğe Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer(Springer, 2013) Yandim, Melis Kartal; Apohan, Elif; Baran, YusufSphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDP-glucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.Öğe Trametes versicolor ile lakkaz üretimi ve renk giderimi: Taguchi ve Box-Behnken yöntemlerinin uygulaması(2014) Gedıklı, Serap; Çelik, Pınar Aytar; Şahin, Yeliz Buruk; Apohan, Elif; Çabuk, Ahmet; Yeşilada, Özfer; Burnak, NimetullahAmaç: Çalışmanın amacı, batık fermentasyon koşulları altında Trametes versicolor 2008001 suşu ile lakkaz üretimini araştırmaktır. Daha sonra üretilen lakkaz enzimi ile Box-Behnken metodu kullanılarak boyar madde dekolorizasyonunun optimizasyonu amaçlanmıştır.Metod: Yüksek aktivitede lakkaz enzimi üretimi için en uygun kültür koşulları, Taguchi yöntemi kullanılarak belirlenmiştir. Deneyler L27 (35) ortogonal dizi düzeni ile 5 faktör (glukoz, maya özütü, CuSO4, inokulum miktarı ve pH) 3 düzey kullanılarak tasarlanmıştır. Daha sonra, elde edilen ham lakkaz ile Reaktif Mavi 49'un yüksek renk giderimi için en uygun koşullar, Box-Behnken yöntemi kullanılarak incelenmiştir.Bulgular: Yüksek aktiviteye sahip lakkaz enziminin üretimi için en uygun kültür koşulları, 2 g L-1 glukoz, 5 g L-1 maya özütü, 2mM CuSO4, %4 inokulum miktarı ve pH 5,5 olarak belirlenmiştir. Maya özütü en etkili faktördür, bunu CuSO4, inokulum miktarı, glukoz ve pH takip etmiştir. Bu koşullar altında tahmini değerler ile deneysel değerler arasında uyum söz konusudur. Önerilen sonuçlar, pH'nın 2,95, başlangıç boya konsantrasyonunun 55,6 mg L-1, enzim miktarının 0,76 mL ve reaksiyon süresinin 46,91 dakika olduğu koşullarda en yüksek Reaktif Mavi 49 renk gideriminin %98 olduğunu göstermiştir. Bu istatistiksel optimizasyon stratejisinin geçerliliği ve uygulanabilirliği, tahmini ve deneysel değerler arasındaki ilişki ile doğrulanmıştır.Sonuç: Sonuçlar Taguchi yönteminin lakkaz üretim sürecinde optimizasyon için kullanılabileceğini göstermiştir. Ayrıca en uygun koşullardaki renk giderimi deneylerinin sonuçlarına göre, Trametes versicolor 2008001 ile üretilen lakkaz enzimi etkin bir şekilde enzimatik renk gideriminde kullanılabilirÖğe Vinas ve zeytin yağı fabrikası atık suyunun değerlendirilmesi ve biyolojik iyileştirilmesinde beyaz çürükçül fungus peletlerinin kullanımı(İnönü Üniversitesi, 2007) Apohan, ElifAlkol fabrikası atık suyu (vinas) ve zeytin yağı fabrikası atık suyu (ZYFA) önemli oranda çevre kirliliğine neden olmaktadır. Her iki atık suyun organik madde içeriği yüksektir ve bu nedenle arıtılmaları veya değerlendirilmeleri gerekmektedir. Atık suların enzim üretiminde değerlendirilmesi ve bu süreçte biyolojik iyileştirilmenin sağlanması çevre kirliliğinin önlenmesi anlamına gelmektedir. Bu çalışmada, Funalia trogii ve Trametes versicolor peletlerinin atık su ortamlarında enzim üretim yetenekleri test edilmiştir ve enzim üretiminde etkili olan faktörler optimize edilmiştir. Lakkaz aktivitesini artırmak için çeşitli kaynaklar (glikoz, maya özütü, bakır, peynir altı suyu) atık su ortamlarına eklenerek tekrarlı kesikli süreçte lakkaz üretim verimi incelenmiştir. Tutuklanmış ve serbest fungusların lakkaz üretim yeteneği ve verimi de tekrarlı kesikli süreçte karşılaştırılmıştır. Fungus peletlerinin biyolojik iyileştirmesini test etmek için işlem görmüş ve görmemiş atık suyun kimyasal oksijen istemi (KOİ) karşılaştırılmıştır. Her iki atık su ortamlarında elde edilen lakkazın sıcaklık kararlılığı da belirlenmiştir. Glikoz, maya özütü, peynir altı suyu ve bakır, peletlerin kararlılığını ve lakkaz üretim yeteneklerini farklı etkilemiştir. Her iki atık suya bakır eklenmesi enzim aktivitesini arttırmıştır (4-10 kat). F. trogii peletleri vinasın ve ZYFA'nın KOİ içeriğini sırasıyla %32 ve %33 oranında gidermiştir. T. versicolor peletleri de bu atık suların KOİ içeriğini azaltmıştır. Bu araştırma, fungus peletlerinin bu atık suların biyolojik iyileştirilmesinde kullanılabileceğini ve peletlerin bazı belirli şartlarda lakkaz üretiminde kullanılabileceğini göstermiştir.Öğe Yeni Benzimidazol Metal Kompleks Bileşiklerinin Sitotoksik/Apoptotik ve Antimikrobiyal Aktivitelerinin Araştırılması(2016) Apohan, Elif; Yesılada, Özfer; Küçükbay, Hasan; Kaya, Emin; Yılmaz, ÜlküKanser, dünyada ölümlere yol açan önemli nedenlerden biridir. Kronik myeloid lösemi (KML) letal ve klonal bir kök hücre hastalığıdır. Kan ve kemik iliğinin yavaş seyirli kanseridir. KML, lösemilerin yaklaşık dörtte biridir ve her 100.000 kişiden 1-2’sinde hastalık görülür. Son yıllarda KML tedavinin yaşam boyu sürmesi nedeniyle tedavi maliyeti oldukça yüksek ve hücreler imatinibe karşı direnç geliştirmektir ve ayrıca hastalığın ileri evrelerinde başarı şansı daha düşüktür. Akciğer kanseri, kanserle ilişkili ölümlerden en yaygın olanlardan biridir. Tüm kanser ölümlerinin yaklaşık üçte birini oluşturur. Tüm akciğer kanseri hastalarının sadece %15’i tanıdan sonra 5 yıl ve daha fazla yaşamaktadır. Hücreler uygulanan kemoterapiye direnç geliştirir ve böylece ölüme neden olur. Günümüzde uygulanan terapötik müdahaleler bu hastalığın epidemik oranı üzerinde az etkiye sahiptir ve ölüm oranı %85-90 arasındadır. Benzimidazol iskeleti, biyolojik aktif moleküllerde kimyasal işlevselliği gösteren kullanışlı yapısal bir motiftir. Benzimidazoller; antikanser, antibakterial, antifungal, anti- inflammator ve antioksidant aktivite göstermektedir. Benzimidazoller, vitamin B12 ve türevleri ile çeşitli metaloprotenleri de kapsayan biyolojik moleküllerde olduğu gibi geçiş metal iyonlarında önemli bir ligantdırlar. Bu nedenle geçiş metali tuzlarının benzimidazol türevleri bazı önemli biyolojik moleküller için model yapı olarak yaygınca çalışılmaktadır. Biyolojik olarak önemli ligantların metal kompleksleri bazen serbest liganttan çok daha etkindirler. Bu çalışmada, kobalt ve çinko bağlı benzimidazol kompleks bileşikleri kullanılmıştır. Sentezlenen bileşiklerin yapıları 1 H, 13 C, NMR, IR, spektroskopik yöntemleri ve elementel analiz yöntemi kullanılarak aydınlatılmıştır. Yeni sentezlenmiş 14 bileşik içinden üç tanesinin (1, 4 ve 5 nolu) akciğer kanseri hücreleri (A549) üzerine cisplatinden daha güçlü sitotoksik aktiviteye sahip olduğu tespit edilmiştir. Aynı zamanda bu üç bileşiğin sağlıklı akciğer epitel hücresi olan BEAS2B hücreleri üzerine cisplatinden daha az sitotoksik etkisinin olduğu belirlenmiştir. Kronik myeloid lösemi hücreleri (K562) üzerine ise 1. ve 5. bileşikler, imatinibden daha güçlü sitotoksik etkiye sahipken sağlıklı lenfoid hücreleri üzerine imatinibden daha düşük sitotoksik aktiviteye sahip olduğu tespit edilmiştir. Bu bileşikler için patent başvurusunda bulunulmuştur. Bileşikler ile cisplatin veya imatinibin birlikte kullanıldığında sinerjistik etki belirlenmedi. Bileşiklerin A549 hücrelerinde kaspaz 3 aktivitesini artırıcı etkisi olmadı. Diğer yandan 5. bileşik K562 hücrelerinin kaspaz 3 aktivitesini indükledi. Yüksek sitotoksik etki gösteren 1, 4 ve 5. bileşikler aynı zamanda kullanılan mikroorganizmalara yüksek antimikrobiyal aktivite de göstermiştir.
