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Item 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-4078-2020Objectives: 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.Item 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-9080-2019Objectives: 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.Item 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, NamikItem 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-9966-2020Background 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.