M Ramazan Yigitoglu

Turgut Özal University, Engüri, Ankara, Turkey

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Publications (8)15.79 Total impact

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    ABSTRACT: The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4-/-, Adamts5-/-, and wt mice but not in the sham-operated group. By contrast Adamts4-/- and Adamts5-/- mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4-/- mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4-/- or Adamts5-/- mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.
    BioMed Research International 01/2014; 2014:693746. · 2.88 Impact Factor
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    ABSTRACT: The increasing prevalence of both asthma and obesity are major health problems. Recent studies established a possible link between obesity and asthma; however, the underlying mechanism is not clear. The aim of the study was to analyze the prevalence of metabolic syndrome in postmenopausal subjects with asthma and search the interactions between adipokines, metabolic syndrome, and asthma. A total of 45 female patients (57.5 ± 13.9 years) with asthma and 30 healthy subjects (59.6 ± 12.8 years) in postmenopausal status were enrolled in this study. For the diagnosis of metabolic syndrome, modified World Health Organization diagnostic criteria were used. Blood levels of glucose, lipid profile, HbA1c, insulin, CRP, leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8 and plasminogen activator inhibitor-1 (PAI-1) were measured. The mean body mass index was 29.6 ± 5.4 for asthma patients and 28.2 ± 5.3 for the control group. The incidence of metabolic syndrome was found as 26 % for both groups. Insulin resistance as calculated by homeostasis model assessment (HOMA-IR) and fasting insulin levels were significantly higher in asthma patients (p < 0.001 for both parameters). Leptin levels were significantly higher (p = 0.001) and adiponectin levels were lower (p = 0.029) in asthma patients compared to controls. We concluded that although incidence of obesity and metabolic syndrome was not higher in postmenopausal asthma patients than controls, there was an impairment of glucose metabolism and altered adipokine levels in asthma patients.
    Inflammation 06/2013; · 2.46 Impact Factor
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    ABSTRACT: ADAMTS (adisintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.
    Neuroscience Letters 04/2013; · 2.03 Impact Factor
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    ABSTRACT: Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at μM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.
    Nutrition and Cancer 01/2013; 65(4):515-26. · 2.70 Impact Factor
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    ABSTRACT: The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor-κB (NF-κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF-κB in IL-1β-induced ADAMTS9 expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1β. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL-1β. For the effects of NF-κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL-1β. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real-time polymerase chain reaction (PCR) was performed on cDNA samples. There was a significant difference between control and stimulated cells in terms of ADAMTS9/β-actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-κB inhibitors, led to a decrease in the ratio of ADAMTS9/β-actin. As a conclusion, the pathways MAPK and NF-κB were thought to be responsible pathways for the induction of ADAMTS9 gene. Copyright © 2012 John Wiley & Sons, Ltd.
    Cell Biochemistry and Function 11/2012; · 1.85 Impact Factor
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    ABSTRACT: Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.
    Cell Biochemistry and Function 03/2012; 30(5):438-43. · 1.85 Impact Factor
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    ABSTRACT: The relation between nonalcoholic steatohepatitis and iron metabolism is still controversial. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage, and necroinflammation mediated by various cytokines. Sixty patients were diagnosed with NASH were included in the study, and the patient group was divided into three subgroups. Iron metabolism markers, inflammatory cytokines, including TNF-α, IL-6 and IL-8, MDA and nitric oxide levels were measured. Serum ferritin, inflammatory cytokines, and oxidative stress markers were significantly higher in the patient group. Among three patient groups, divided according to the results of ultrasonic examination, there were significant changes with regard to these parameters. The study results suggest that liver iron and fat accumulation, oxidant stres, and inflammatory cytokines are closely related. Therefore, levels of serum ferritin, MDA, IL-6, TNF-α and IL-8 could represent the indices of activity and progression of NASH.
    Clinical biochemistry 12/2011; 44(17-18):1375-9. · 2.02 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.