0mer faruk hatipoglu | Turgut Ozal University (original) (raw)

Papers by 0mer faruk hatipoglu

European Journal of Cancer, Jul 5, 2014

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-ind... more ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression....

ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) ... more ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes, with aggrecan-degrading activity. The nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors related to Rel/NFκB family whose activation is controlled by calcineurin. The inhibition of aggrecan degradation likely plays a protective role in the prevention of cartilage collagen breakdown. Recently, an NFAT inhibitor peptide, VIVIT, was developed based on the conserved calcineurin docking site of the NFAT family. The presence of putative NFAT binding elements (NBE) in the ADAMTS9 promoter region prompted an investigation of whether NFAT is one of the activators for ADAMTS9 upon IL-1 stimulation. To test the possibility regarding whether NFAT mediates the induction of ADAMTS9, real-time PCR was done using inhibitors for NFAT, FK506 and 11R-VIVIT. ADAMTS9 expression was decreased to nearly 40-50% by 1 μM of 11R-VIVIT. In addition, western blott was d...

Objective: ADAMTS9, known as a cytokine-inducible gene, has binding sites for nuclear factor-κB (... more Objective: ADAMTS9, known as a cytokine-inducible gene, has binding sites for nuclear factor-κB (NF-κB) in its promoter region. NF-κB dimers bind a family of 9-11 bp of this DNA- binding sites (DNA sequences) known as κB sites. NF-κB is involved in cell proliferation, differentiation and apoptosis by inducing and repressing gene expression. Since interleukin 1-(IL1-) is known to exert numerous effects on cartilage metabolism through the NF-κB pathway, we speculated about the putative involvement of NF-κB in the induction of ADAMTS9 by IL1- in human chondrocytes. Methods: Here, we investigated whether IL1-- induced expression of ADAMTS9 is mediated by the NF-κB p65 subunit. Human chondrocytes were cultured in the presence or absence of IL1-with our without specific inhibitors of selected signaling pathways.ADAMTS9 mRNA levels were analyzed by Real time PCR. NF-κB sites were cloned into a luciferase reporter vector and analyzed in transient transfection. The Chromatin immunopr...

Acta medica Okayama, 2009

International journal of clinical and experimental medicine, 2013

Acne, a chronic inflammatory skin disease, can be seen at any age but it most often occurs in ado... more Acne, 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...

Visfatin, characterized in 1994 is an adipokine (adipocytokines). It was secreted by not only vis... more Visfatin, characterized in 1994 is an adipokine (adipocytokines). It was secreted by not only visceral adipose tissue but also by several tissues. First, visfatin with insulin-mimetic activity has been implicated in the insulin resistance. Finally, it was understand that visfatin involves in several pathological processes like inflammation. The degradation of aggrecan by inflammation induced aggrecanases is a key process for diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). Aggrecanases-1 and -2, called ADAMTS-4 and -5 respectively are members of a disintegrin and metalloproteinase with thrombospondin motifs enzyme family. The aim of this study was to investigate the potential role of visfatin in aggrecan destruction. Human articular chondrocytes were stimulated with visfatin at 10, 25, 50, 100, 250 and 500 ng/ml doses. Total RNA was isolated and reverse-transcribed by random primer. The aggrecanases-1 and -2 genes expression were analyzed and standardized by β-act...

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of peptidases... more A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of peptidases. They comprise 19 members, and have several vital functions in organism. ADAMTS-9 with aggrecanolytic activity is responsible for the degradation of the articular cartilage components like aggrecan. Adiponectin is the most abundantly secreted adipokines (adipocytokines), and the characteristic of adiponectin is controversial. It was assumed that adiponectin has anti-inflammatory effect. However, recent studies showed the inflammatory features of adiponectin. It was aimed to evaluate the effect of adiponectin on ADAMTS-9 gene expression in human chondrocytes. Human articular chondrocytes were cultured and exposed by adiponectin at 1, 4, 8 and 12 µg/ml doses. At the end of the incubation, total RNA was reverse-transcribed by random primer. The expression levels of the ADAMTS-9 and β-actin genes were determined using real-time polymerase chain reaction. The ADAMTS-9 gene expression was fou...

The cloning of leptin initiated to explore new functions of adipose tissue. The studies revealed ... more The cloning of leptin initiated to explore new functions of adipose tissue. The studies revealed that adipose tissue like endocrine organ involves in critical roles by secreting adipokines. Among them, leptin is the most studied and characterized adipokine, and involves in several pivotal processes including inflammation. The degradation of articular cartilage components by aggrecanases-1 and -2 (called also a disintegrin and metalloproteinase with thrombospondin motifs -4 and -5) is a key event for arthritic diseases. The catabolic effect of leptin on articular cartilage degradation by increasing aggrecanases was established, but the pathways involved in this upregulation have not been elucidated. It was aimed to investigate putative molecular pathways involving in the upregulation of aggrecanases by leptin. The cultured human articular chondrocytes were incubated with SB203580 (a specific inhibitor of p38) and subsequently recombinant human leptin. At the end of the 48 hours, tota...

Objective: ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs1) is an inflam... more Objective: ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs1) is an inflammatory-induced gene. We have previously reported ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether 3’-untranslated region (UTR) affects its mRNA stability. The 3’-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that 3’-UTR may regulate its stability. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1-3’-UTR destabilized transfected EGFP mRNA expression. These data demonstrated that ADAMTS1-3’-UTR may regulate the expression of ADAMTS1 mRNA. Methods: The expression of ADAMTS1 mRNA was examined in Cos7 stimulated by TNFα and LPS. To examine the effect of 3’-UTR for the decay of RNA, we amplified the 3’-UTR of human ADAMTS1 mRNA by PCR. Two constructs, PmaxLong and PmaxShort, were created, the Long consisting of AUUUA motif absent in the Short. For the mRNA stability assay, ce...

European Journal of Cancer

The irreversible destruction of extracellular matrix (ECM) components is key process for inflamma... more The irreversible destruction of extracellular matrix (ECM) components is key process for inflammatory and autoimmune diseases. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), a family of metallopeptidase involve in several physiological and pathological processes including degradation of matrix components. Resistin, an adipokine was characterized in 2001. The involvement of resistin in several biological processes was established before. However, the putative catabolic role of resistin on the components of ECM was not elucidated in detail. The aim of study was investigate to ADAMTS-4 gene expression level in SW1353 chondrosarcoma cell line after resistin induction. The SW1353 chondrosarcoma cell line was plated at 37 oC in a humidified atmosphere of 5% CO2. After confluent, the cell was stimulated by resistin at 100 ng/mL dose, and incubated for 6, 12, 24, and 48h. At the end of the stimulation, the total RNA was isolated, and reverse transcribed into cDNA u...

Journal of B.U.ON. : official journal of the Balkan Union of Oncology

The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Fou... more The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Foundation- 7) breast cancer cells, as it is known to exert an antitumor effect on the expression and regulation of ADAMTS1, 3, 10 and the p53 gene in breast cancer cells. MFC-7 cells were cultured and subjected separately to various doses (1, 5 and 7.5 μg /mL) hypericin. After 24 hrs, RNA was isolated and transcribed into cDNA. Expression analysis was performed by real time (RT)-PCR and cell survival was determined by the XTT assay. While the expression of ADAMTS1 in MFC-7 cells decreased to 0.04-fold after exposure to 1 μg /mL hypericin, the expression increased by 5.6- and 36-fold with 5 and 7.5 μg/mL, respectively. Furthermore, ADAMTS3 expression in MCF7 cells increased 3.9-fold with the use of 5 μg /mL of hypericin. These concentrations of hypericin did not lead to significant changes in the expression of ADAMTS10 and the p53 gene. Viability of cancer cells as evaluated by the XTT assa...

Cell Biology International, 2014

Elucidation of the causes of inflammation has vital importance in the development of new approach... more Elucidation 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-ĸB, and PI3) involved in leptin-induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h, 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 1000 ng/mL doses for 48 hours, and MAPKs (p38, JNK, and MEK) and NF-ĸB 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-ĸB signaling pathways.

TURKISH JOURNAL OF MEDICAL SCIENCES, 2014

Aim: Prostate cancer is the most commonly diagnosed malignancy and the second most common cause o... more Aim: Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathological processes such as cancer. In this study, the association between TIMP-2 (-418 G/C) and MMP-2 (-1306 C/T) polymorphisms and prostate cancer in the Turkish population was investigated.

Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways, 2011