Browsing by Author "Atac, Fatma Belgin"

Now showing 1 - 10 of 10

Beta-Cell Golgi Stress Response to Lipotoxicity and Glucolipotoxicity: A Preliminary Study of a Potential Mechanism of Beta-Cell Failure in Posttransplant Diabetes and Intraportal Islet Transplant
(2022) Tutuncu, Neslihan Bascil; Verdi, Hasibe; Yalcin, Yaprak; Cebi, Pinar Baysan; Kinik, Sibel; Tutuncu, Tanju; Atac, Fatma Belgin; 0000-0002-1816-3903; 0000-0002-9337-9106; 0000-0002-9141-9987; 35791832; ABG-5027-2020; ABB-4078-2020
Objectives: Lipotoxicity and glucolipotoxicity are among the most important triggers of beta-cell failure in patients with type 2 and posttransplant diabetes. Because the Golgi apparatus is a vital organelle in secretory cells like beta cells, its behavior under stress conditions determines the cell's functional capacity.Materials and Methods: To mimic lipotoxicity and glucolipotoxicity as metabolic stresses for beta-cell failure, rat insulinoma INS-1E cells were treated with palmitic acid, glucose, or both. Cells were cultured in the presence of 5.0, 16.7, or 33 mM glucose with or without 0.5 mM palmitic acid for 8, 16, 24, and 48 hours. Incubation in the presence of any of the 3 concentrations of glucose with 0.5 mM palmitic acid provided glucolipotoxicity. In addition to the endop-lasmic reticulum stress marker (Hspa5), we evaluated changes in Golgi function under experimental metabolic stresses. In doing this, we measured expression levels of the genes coding Golgi structural proteins (Acbd3, Golga2, and Arf1), Golgi glycosylation enzymes sialyltransferaz10 and sialyltransferase 1 (St3gal1), and Golgi stress mediators (Creb3 and Arf4).Results: Golgi responded to lipotoxicity and glucolipotoxicity by increasing the expression of St3gal1 (P = .05 in both conditions) and Creb3 (P = .022 and P = .01, respectively). The Arf4 gene transcript also increased in glucolipotoxic media (P = .03). Glucotoxicity alone did not induce a change in the transcript levels of Creb3 and Arf4. Lipotoxicity and glucolipotoxicity induced Creb3 and Arf4 expression, which are important Golgi stress response mediators leading to apoptosis.Conclusions: This preliminary study showed that the Golgi stress response is important in lipotoxic and glucolipotoxic conditions in terms of beta-cell failure. Solving the mystery of intracellular molecular mechanisms leading to beta-cell dysfunction is crucial to understanding the pathophysiology of posttrans-plant diabetes and most probably the failure of intraportal islet transplants in the long term.
Endoplasmic Reticulum Stress Response in Non-Alcholic Fatty Liver Disease: Sophisticated Pathways
(2023) Etik, Digdem Ozer; Verdi, Hasibe; Atac, Fatma Belgin; https://orcid.org/0000-0001-6868-2165; V-5499-2017; ABG-9966-2020
Non-alcoholic fatty liver disease comprises a broad spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. The multiparallel hypothesis suggests that steatohepatitis is the result of numerous conditions acting in parallel, including form genetic susceptibility, lipotoxicity, disturbed gut microbiata to mitochondrial dysfunction, and endoplasmic reticulum(ER) stress. The unfolded protein response as the ER stress response is coordinated primarily by ER transmembrane stress transducers which is a defensive response initially activates the cell to recover from stress or adapt to stress. It reduces the secretory protein load, enhances protein folding and increases clearance capacity by promoting autophagy and ER-associated degradation. However, if these attempts fail or the ER stress gets prolonged, it will induce cell death programs to eliminate the stressed cells. In recent years, ER stress response has been identified as a crucial mechanism in steatohepatitis by leading improper lipid biosynthesis, inflammation, and autophagy or apoptosis.
Endothelial nitric oxide synthase gene polymorphisms in patients with slow coronary flow
(2017) Tekin, Abdullah; Sezgin, Nurzen; Atac, Fatma Belgin; Verdi, Hasibe; Sezgin, Alpay Turan; 0000-0002-5658-870X; 0000-0001-6868-2165; 0000-0003-0591-009X; 29201435; ABG-9940-2020; ABD-7304-2021; ABG-9966-2020
Background and aims: The aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NOx) concentrations and eNOS gene polymorphisms was also assessed. Materials and methods: The intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61). Results: Plasma NOx level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NOx concentrations with respect to the relevant genotypes were found insignificant. Discussion and conclusion: Plasma NOx is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.
Endothelial Nitric Oxide Synthase Polymorphism Influences Renal Allograft Outcome
(2014) Uyar, Murathan; Sezer, Siren; Ozdemir, Fatma Nurhan; Kulah, Eyup; Arat, Zubeyde; Atac, Fatma Belgin; Haberal, Mehmet; https://orcid.org/0000-0002-7326-8388; https://orcid.org/0000-0002-5682-0943; https://orcid.org/0000-0001-6041-4254; https://orcid.org/0000-0001-6868-2165; https://orcid.org/0000-0002-3462-7632; 24372826; AAK-5313-2021; JYQ-2550-2024; AAK-1697-2021; AAJ-5764-2021; ABG-9966-2020; AAJ-8097-2021
BackgroundAtherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three- and five-yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism. MethodsSeventy-one male and 35 female patients (age: 34.911.2yr) who underwent living-related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre- and post-transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated. ResultsPatients with the bb allele of eNOS gene had a lower prevalence of post-transplant third year (12.6% and 38.5%, p=0.005) and fifth year IF/TA (46.6% and 82.3%, p=0.02) and a lower incidence of five-yr graft failure (35.4% and 55.6%, p<0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p=0.01, RR: 29.72, and p=0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered. ConclusionsWe concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.
Is there any association between thrombotic risk factors and veno-oclusive disease in childhood allogeneic hematopoietic stem cell transplantation?
(2019) Cihan, Meric Kaymak; Atac, Fatma Belgin; Bilir, Ozlem Arman; Aksu, Tekin; Kanbur, Serife Mehtap; Ozbek, Namik
Lack of association between MMP13 (rs3819089), ADAM12 (rs3740199-rs1871054) and ADAMTS14 (rs4747096) genotypes and advanced-stage knee osteoarthritis
(2021) Haberal, Bahtiyar; Simsek, Ekin Kaya; Cebi, Hatice Pinar Baysan; Tuc, Ozer; Verdi, Hasibe; Atac, Fatma Belgin; 0000-0002-1668-6997; 0000-0002-9141-9987; 0000-0002-2228-6893; 0000-0003-0591-009X; 34145804; W-9080-2019
Objectives: The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). Patients and methods: A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the KellgrenLawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample. Results: The most common nucleotides in both the control and patient groups were CG for rs3740199 and CT for rs1871054 in the ADAM12 gene, and the most common nucleotides in alleles were GG for MMP13 rs3819089 and AA for ADAMTS14 rs4747096. No statistically significant relationship was detected between the gene polymorphisms and advanced OA. Conclusion: The study results suggest that ADAM12 rs3740199 and rs1871054, MMP13 rs3819089, and ADAMTS14 rs4747096 polymorphisms have no relationship with knee OA susceptibility in the Turkish population. However, as this is the first study to investigate the relationship between the SNPs of ADAM12, ADAMTS14, and MMP13 genes and the development of OA in the Turkish population, it would contribute to our understanding of the molecular bases of OA.
Multidrug Resistance 1 (MDR1) 3435C/T Genotyping in Childhood Drug-Resistant Epilepsy
(2014) Saygi, Semra; Alehan, Fusun; Atac, Fatma Belgin; Erol, Ilknur; Verdi, Hasibe; Erdem, Remzi; https://orcid.org/0000-0002-8522-5078; https://orcid.org/0000-0001-6868-2165; https://orcid.org/0000-0002-3530-0463; https://orcid.org/0000-0003-0591-009X; https://orcid.org/0000-0002-7537-2170; 23465586; AAB-1203-2021; ABG-9966-2020; AAK-4825-2021; ABG-9940-2020
Introduction: A mutation at nucleotide position 3435 in exon 26 of the multidrug resistance 1 (MDR1) gene is the most frequently studied polymorphism in relation to multidrug resistance. However, there are conflicting data as to whether the CC or TT genotype of the 3435C>T polymorphism is associated with drug resistance. Methods and results: We investigated the association between this polymorphism in drug-resistant childhood epilepsy by comparison with drug-responsive patients. In total, 59 patients with drug-resistant epilepsy, defined as having four or more seizures within a 12-month period while using three or more AEDs, 60 children with drug-responsive epilepsy who had remained seizure-free for 12 months on their current AED regimen and 76 healthy children were involved in this study. Genotype frequencies in drug-resistant patients were as follows: 32.2% CC, 44.1% CT, 23.7% TT; in the drug-responsive group: 20.0% CC, 50.0% CT, 30.0% TT; in the control group: 24.3% CC, 50.0% CT, 25.7% TT. Comparison of drug-resistant and drug-responsive patients revealed no significant difference in genotype frequency. The findings of the epilepsy patients were not significantly different from those of the healthy control subjects. Conclusions: Our study does not support any significant association between the MDR1 polymorphism and drug-resistant childhood epilepsy. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
The Relationship of Recurrent Aphthous Stomatitis and Helicobacter Pylori, Cytokine Gene Polymorphism and Cobalamin
(2015) Yakar, Tolga; Serin, Ender; Cosar, Arif Mansur; Tas, Didem Arslan; Atac, Fatma Belgin; 0000-0002-0138-6107; 26039006; AAM-7281-2021
Background/Aims: The aim of the present study was to investigate whether Helicobacter pylori causes or triggers recurrent aphthous stomatitis (RAS) through cytokine gene polymorphism and/or cobalamin deficiency. Materials and Methods: Thirty-six patients with RAS and 130 patients without RAS were genotyped for IL-1 beta (-511C/T) and IL-6 (-174G/C) and evaluated for H. pylori infection and serum cobalamin level. Results: The patient groups according to RAS had similar rates of H. pylori gastritis and interleukin genotypes/alleles, and there was a non-significant difference between serum cobalamin levels (p>0.05). RAS patients with H. pylori gastritis showed a higher frequency (51.9%) of GC IL-6 genotype than RAS patients without H. pylori gastritis (11.1%) (p=0.036). Non-GG genotype and C allele were increased in patients without RAS and with H. pylori gastritis (p<0.05). Patients with H. pylori gastritis showed a lower value of serum cobalamin without statistical significance, although this difference was more prominent in RAS patients (p=0.07). Conclusion: The carriage of the C allele of IL-6 may lead a susceptibility to chronic gastric inflammation after contamination with H. pylori. If H. pylori infection is justified as a predisposing factor for RAS and its severity by further studies, we can speculate that subjects with genetic susceptibility to this infection may benefit from H. pylori eradication treatment with respect to RAS.
The Role of Parkin in Rat Pancreatic Beta Cells Fate
(2023) Verdi, Hasibe; Cebi, Hatice Pinar Baysan; Yalcin, Yaprak Yilmaz; Ozkan, Tulin; Mehtap, Akcil; Sunguroglu, Asuman; Atac, Fatma Belgin; 0000-0002-9337-9106; 0000-0001-7693-0958; 37715413; ABB-4078-2020; AAQ-4882-2020
Parkin is a member of the mitochondrial quality control system that plays a major role in mitophagy. Although the loss of function mutations in the Parkin gene has been associated with the Familial Parkinson's pheno-type, research in recent years points out that Parkin's function is not limited to neurodegenerative diseases. Parkin's function impressing key cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, makes it an important player in the maintenance of cellular homeostasis. In this study, we investigated whether Parkin affects cell viability and ER stress responses under lipotoxic conditions in INS-1E cells. Our results may suggest that silencing Parkin may affect autophagy in addition to apoptosis. We also showed that Parkin may have a protective effect against lipo-toxic effects in INS-1E cells. Consistent with previous studies, we observed that stress responses were different for high and low palmitic acid doses. The Parkin being inhibited under high-dose PA treatment and active under low-dose PA treatment indicate that regulation of stress responses is controlled by environmental conditions. Our preliminary findings may suggest that in low lipotoxic conditions, Parkin affects the ER stress response by modulating Chop activity and Ca2+ release from the ER to the cytoplasm.
TGF-β1 Genotype in Pediatric Migraine Patients
(2015) Saygi, Semra; Alehan, Fusun; Erol, Ilknur; Yalcin, Yaprak Yilmaz; Atac, Fatma Belgin; Kubat, Gozde; 0000-0002-3530-0463; 0000-0002-9337-9106; 0000-0002-8522-5078; 0000-0001-6868-2165; 24619148; AAK-4825-2021; ABB-4078-2020; AAB-1203-2021; ABG-9966-2020
There is no information about the role of transforming growth factor-beta 1 (TGF-1) in the pathogenesis of pediatric migraine. This study included 100 consecutive children and adolescents in whom migraine was diagnosed and 88 healthy children and adolescents. The isolated genomic DNA was used as a template for TGF-1 (-800G/A, -509C/T, 869T/C [codon 10] and 915G/C [codon 25]) genotyping. The allelic frequency of 509C/T was significantly different between control and migraine without aura patients (P = .04). Codon 10 C/T genotypic and C10 C allelic frequency of TGF-1 polymorphisms were significantly higher in migraine and migraine without aura patients versus healthy controls (P = .00; P = .00). To our knowledge, this is the first report dealing with the relationship between TGF-1 genotype and migraine in the pediatric age group. Further studies related to this subject are needed, along with a search for new therapeutic agents with anti-inflammatory properties.