Epigenetic Mechanisms and Cancer

İlk defa 1940ların başında Condrad Hal Waddington tarafından ortaya atılan epigenetik kavramı, DNA dizilimini değiştirmeden gen ifadesini etkileyen kalıtılabilir değişiklikler olarak tanımlanabilir. Yapılan araştırmalarla epigenetik mekanizmaların birçok biyolojik olayda ve kanser gibi hastalıklarda önemli görevler ifa ettiği bulunmuştur. Bu derlemede literatürdeki epigenetik mekanizmalar ve bunların kanserle olan ilişkileri hakkında bilgiler özetlenmiştir.Epigenetics, proposed by Condrad Hal Waddington at the begining of the 1940 describes heritable changes that affect gene expression without changing DNA sequencing. After researches, it has been found that the epigenetics modifications perform important task in many biological processes and diseases like cancer. In this review we summarize the information in literature related with epigenetic mechanisms and their relationship with cancer

Polymorphisms in the promoters of MMP-2 and TIMP-2 genes in patients with acne vulgaris

Hatipoglu, Omer Faruk/0000-0002-1012-001X; Yaykasli, Kursat/0000-0001-7550-6370; Kaya, Ertugrul/0000-0003-0081-682XWOS: 000327588200015PubMed: 24260605Acne, a chronic inflammatory skin disease, can be seen at any age but it most often occurs in adolescents and young people. Several factors, including increased sebum production, abnormal cornification of the pilosebaceous units, proliferation of Propionibacterium acne, and extracellular matrix (ECM) remodeling, are thought to be associated with the pathogenesis of the acne. The remodeling of the ECM is regulated by a balance between matrix metalloproteinases (MMPs) and their inhibitors called tissue inhibitors of metalloproteinases (TIMPs). The current study investigated the potential association between MMP-2 (-1306 C/T) and TIMP-2 (-418 G/C) polymorphisms and the risk for acne in a Turkish population. The study was conducted with 85 subjects who presented to the Dermatology Department of Duzce University Hospital. DNA was isolated from 2 ml of peripheral blood taken from each subject, and their genotypes were analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CC, CT, and TT genotypes for MMP-2 (-1306 C/T) polymorphism were similar between the patient and control group (24 [55.8%], 17 [39.5%], and 2 [4.7%], respectively, vs. 21 [50%], 18 [42.9%], and 3 [7.1%], respectively). However, the distribution of the GG, GC, and CC genotypes for TIMP-2 (-418 G/C) polymorphism were different between the patient and control group (30 [69.8%], 9 [14.8%] and 4 [9.3%], respectively, vs. 26 [61.9%], 14 [33.3%], and 2 [4.8%], respectively). The results demonstrated that the TIMP-2 (-418 CC) genotype was nearly two times more common in the patient group compared to the control group (p=0.686, OR=1.45). It may be possible that the TIMP-2 (-418 CC) genotype increases the tendency to develop acne vulgaris by disrupting the balance between MMPs and TIMPs. Further investigations are needed to clarify more precisely the relationship between acne and MMP-TIMP genes

A Research on the Determination of Aflatoxin M1 Levels in Milk and Dairy Products for Sale in Diyarbakır by ELISA

In this study, the contamination levels of Aflatoxin M1 of 248 sterilized milk, Beyaz, Cecil, Cokelek, Cream, Lor, Van Otlu (herbed), Van Otlu Lavash Cheese and butter samples randomly obtained from selected market and supermarkets from Diyarbakır province center were determined by ELISA method. The average AFM1 contamination value of the cheese samples investigated was 138.65 ng/kg; while the minimum and maximum values were 50 and 595.31 ng/kg, respectively. On the other hand, the average AFM1 value of 13 sterilized milk samples was 52.59 ng/kg; minimum and maximum values were determined as 25.97 and 80.0 ng/kg, respectively. In addition, the average AFM1 value of 18 butter samples was 97.54 ng/kg; the minimum and maximum values were calculated as 50 and 308.13 ng/kg. In the study, the level of AFM1 contamination in the 26 samples of cheese samples were exceeded the limits set by the European Commission for AFM1. In terms of Turkish Food Codex, only 2 cheese samples exceeded the AFM1 tolerance limit. According to the study, the level of AFM1 contamination in the 7 milk samples and 15 butter samples exceeded both the European Commission and Turkish Food Codex AFM1 tolerance limit.Scientific Research Project Coordinatorship of Dicle University Project No: DUBAP-12-MYO-7

Diyarbakır’da Tüketime Sunulan Süt İle Bazı Süt Ürünlerinde Aflatoksin M1 Varlığı Üzerine Bir Araştırma

Bu çalışmada; materyaller, Diyarbakır’da üretildiği ve satıldığı mekanlardan elde edilen; Beyaz Peynir (80), Tuzsuz Beyaz Köy Peyniri (51), Van Otlu Peynir (43), Van Otlu Lavaş Peynir (13), Lor Peynir (12), Tereyağı (18), UHT Süt (13), Çökelek (6), Çeçil Peyniri (7) ve Krem Peynir (5) adetten oluşmaktadır. Toplam 248 adet süt ve ürünlerinin AflatoksinM1(AFM1) bulunma düzeyi, ELISA yöntemi kullanılarak tespit edilmiştir. Ortalama AFM1 değeri yaklaşık olarak; 123,04ng/kg; minimum ve maksimum değerler sırasıyla UHT sütte 25.97ng/kg ve tuzsuz beyaz köy peynirinde 595.31ng/kg olarak tespit edilmiştir. Türk Gıda Kodeksi(TGK)‘nde AFM1 için belirtilen limiti (250ng/kg) aşan örnek sayıları; 27(%10.89) olarak bulunmuştur. AFM1 değeri; 151-250ng/kg olan örnek sayısı; 49(%19.76), 51-150ng/kg olan örnek sayısı; 108(%43.55) ve 0-50ng/kg olan örnek sayısı; 64(%25.81) olarak belirlenmiştir. Analiz sonuçları; Diyarbakır’da tüketime sunulan süt ve ürünlerinin AFM1 yönünden tüketiciler için potansiyel bir risk taşıdığını göstermektedir. Halk sağlığını ciddi bir şekilde tehdit eden AFM1 içeren gıdaların üretilmesinin engellenmesi için; modern süt çiftliklerinin kurulması, uygun yem depolama ve işleme tesislerinin kurulması, üretici ve tüketicilere eğitim seminerleri verilerek bu konuda bilinçlendirilmesi sağlanmalıdır

Diyarbakır'da Geleneksel Yöntemlerle Üretilerek, Tüketime Sunulan Örgü Peynirlerinde Aflatoksin M1 Düzeylerinin ELISA Yöntemiyle Tespit Edilmesi

Bir pasta-filata (fermente telemesi yüksek sıcaklıkta haşlanan) peynir çeşidi olan önemli geleneksel peynirlerimizden Diyarbakır Örgü Peyniri (DÖP); yağ oranı yüksek, az tuzlu (taze tüketilmesi durumunda) ve kolayca liflere ayrılabilen yarı-sert bir peynir çeşididir. Bu çalışmada; bölgesel coğrafi tescili olan ve Diyarbakır’da geleneksel yöntemlerle üretilmiş ve tüketime sunulmuş 184 adet DÖP’ünde, Aflatoksin M1 (AFM1) bulaşma düzeyi, ELISA yöntemi kullanılarak tespit edilmiştir. Çalışılan örneklerde, ortalama AFM1 değeri yaklaşık olarak; 167.58ng/kg; minimum ve maksimum değerler sırasıyla 50 ve 800ng/kg olarak tespit edilmiştir. Türk Gıda Kodeksi (TGK)’inde AFM1 için belirtilen limiti (250ng/kg) aşan örnek sayısı 32 (% 17.39) olarak bulunmuştur. AFM1 değeri; 151-250ng/kg olan örnek sayısı; 53(%28.80), 51-150ng/kg olan; 73(%39.67) ve 0-50ng/kg olan da; 26(%14.13) olarak belirlenmiştir. Analiz sonuçları, Diyarbakır’ın farklı noktalarında satışa sunulan DÖP’ inin AFM1 seviyelerinin tüketiciler için potansiyel bir risk taşıdığını göstermektedir. Söz konusu riskin azaltılabilmesi için, DÖP hammaddesi olan sütün, süt üretim çiftliklerinde yem depolama alanlarının usulüne uygun olarak dizayn edilmesi gerekmektedir. Ayrıca, süt ve peynir üreticileri ile tüketicilerin bu konuda bilinçlendirilmesi için eğitim programları düzenlenmesi önerilmektedir. Öte yandan, söz konusu peynirin yoğun üretildiği yerlerde diğer süt üreticilerine model olması düşüncesiyle, sürdürülebilir modern süt üretim çiftliklerinin kurulması önerilebilir

Dose-dependent effects of adiponectin on ADAMTS-9 gene expression in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370; Hatipoglu, Omer Faruk/0000-0002-1012-001XWOS: 000407091600002PubMed: 28766346OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), comprising of 19 members is a family of peptidases. They have several vital functions in physiological and pathological processes in organisms. ADAMTS-9 has aggrecanolytic activity and is responsible for degradation of aggrecan mainly in articular cartilage. It is known that adiponectin is the most abundantly secreted adipokine (adipocytokines), and the characteristics of adiponectin have not been elucidated yet. It was assumed that adiponectin has anti-inflammatory effect before. However, an inflammatory feature of adiponectin was shown in researches. In our study, the effect of adiponectin on ADAMTS-9 gene expression in primary human chondrocytes was investigated. METHODS: Primary human chondrocytes were exposed to adiponectin at 1, 4, 8 and 12 mu g/ml doses for certain time period. Total RNA was isolated and reverse-transcribed by random primer after incubation. ADAMTS-9 and beta-actin genes expression levels were determined using real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest upregulation of ADAMTS-9 gene expression level was found at 12 mu g/ml dose of adiponectin and 48 h incubation. CONCLUSION: Adiponectin is the key element in the maintenance of cartilage homeostasis. Similarly, the involvement of adiponectin in articular inflammatory diseases was demonstrated in detail. These findings bring adiponectin into central place in the research to develop adiponectin based new therapy methods for arthritic diseases. Together with these findings, our results suggest that adiponectin may be involved in the degradation of articular cartilage by increasing ADAMTS-9 gene expression (Tab. 1, Fig. 3, Ref. 35). Text in PDF www.elis.sk.TUBITAK (The Scientific and Technical Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG/111S218]This study was supported by TUBITAK (The Scientific and Technical Research Council of Turkey), (Project Number: SBAG/111S218)

Dose-dependent effects of adiponectin on ADAMTS-9 gene expression in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370; Hatipoglu, Omer Faruk/0000-0002-1012-001XWOS: 000407091600002PubMed: 28766346OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), comprising of 19 members is a family of peptidases. They have several vital functions in physiological and pathological processes in organisms. ADAMTS-9 has aggrecanolytic activity and is responsible for degradation of aggrecan mainly in articular cartilage. It is known that adiponectin is the most abundantly secreted adipokine (adipocytokines), and the characteristics of adiponectin have not been elucidated yet. It was assumed that adiponectin has anti-inflammatory effect before. However, an inflammatory feature of adiponectin was shown in researches. In our study, the effect of adiponectin on ADAMTS-9 gene expression in primary human chondrocytes was investigated. METHODS: Primary human chondrocytes were exposed to adiponectin at 1, 4, 8 and 12 mu g/ml doses for certain time period. Total RNA was isolated and reverse-transcribed by random primer after incubation. ADAMTS-9 and beta-actin genes expression levels were determined using real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest upregulation of ADAMTS-9 gene expression level was found at 12 mu g/ml dose of adiponectin and 48 h incubation. CONCLUSION: Adiponectin is the key element in the maintenance of cartilage homeostasis. Similarly, the involvement of adiponectin in articular inflammatory diseases was demonstrated in detail. These findings bring adiponectin into central place in the research to develop adiponectin based new therapy methods for arthritic diseases. Together with these findings, our results suggest that adiponectin may be involved in the degradation of articular cartilage by increasing ADAMTS-9 gene expression (Tab. 1, Fig. 3, Ref. 35). Text in PDF www.elis.sk.TUBITAK (The Scientific and Technical Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG/111S218]This study was supported by TUBITAK (The Scientific and Technical Research Council of Turkey), (Project Number: SBAG/111S218)

Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated protein kinases and NF-kappa B signaling pathways in human chondrocytes

Yaykasli, Kursat/0000-0001-7550-6370; Hatipoglu, Omer Faruk/0000-0002-1012-001X; Yaykasli, Emine/0000-0001-6471-0106; Kaya, Ertugrul/0000-0003-0081-682XWOS: 000347382000012PubMed: 25045124Elucidation of the causes of inflammation has vital importance in the development of new approaches for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF-?B, and PI3) involved in leptin-induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000ng/mL doses for 6, 12, 24, and 48h, after which ADAMTS-4, -5, and -9 genes expression were determined by real time-polymerase chain reaction (RT-PCR) and Western Blot methods. The signaling pathways involved in leptin-induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000ng/mL doses for 48hours, and MAPKs (p38, JNK, and MEK) and NF-?B signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS-4, -5, and -9 genes expression via MAPKs and NF-?B signaling pathways.TUBITAK (Scientific and Technical Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG/111S218]This study was supported by TUBITAK (The Scientific and Technical Research Council of Turkey), (Project Number: SBAG/111S218)

Resistin induces a disintegrin and metalloproteinase with thrombospondin motifs-4 gene expression in human chondrosarcoma cell line

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370WOS: 000351589700296

NF-kappa B and MAPKs are involved in resistin-caused ADAMTS-5 induction in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370; Bender, Onur/0000-0003-0691-3508WOS: 000359119100021Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondrocytes. Expression levels of the ADAMTS-5 gene were determined at several resistin doses and durations. Results: Human chondrocytes were activated and associated with upregulated ADAMTS-5 gene expression after exposure to resistin (also known as adipose tissue-specific secretary factor, ADSF). Release of ADAMTS-5 leads to joint cartilage degradation, a key event in the development of arthritic diseases rheumatoid arthritis (RA) and osteoarthritis (OA). Activation of chondrocytes was associated with upregulated NF-kappa B protein levels in a time-dependent fashion. Co-incubation of human chondrocytes with JNK and p38 inhibitors lead to abrogated levels of NF-kappa B, indicating that these MAPKs are important in the activation of chondrocytes after stimulation with resistin. Similarly, ADAMTS-5 expression levels were abrogated when co-incubated with p38, NF-kappa B, JNK, MEK and PI3K inhibitors. Our results demonstrate that resistin, released from adipose tissue, may be involved in the development of RA and OA in obese patients through degradation of joint cartilage via ADAMTS-5 released from activated chondrocytes