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Öğe Epigenetic analysis of heat shock activator complex in the peripheral blood of Parkinson's disease patients and its clinical significance(Turkish Neurosurgical Society, 2024) İnalkac Gemici Y.; Tasci I.; Dundar M.; Ozgen N.; Danis N.; Gozde Gozukara H.; Koc A.Objectives: This study aimed to investigate the methylation changes of related genes in the peripheral blood and their clinical significance in Parkinson's disease (PD) and whether the methylation change of the gene encoding long noncoding RNA was different in the blood of patients and controls. Patients and methods: This prospective cross-sectional, controlled study was conducted with 45 participants (22 males, 23 females; mean age: 60.7±5.9 years; range, 53 to 75 years) between June 2020 and June 2021. Drug-naive patients diagnosed with PD were included in this study. Those with PD and a Mini-Mental State Examination (MMSE) score >23 were defined as Group 1 (n=15), and those with PD and an MMSE score ?23 were defined as Group 2 (n=15). Controls were included in Group 3 (n=15). The methylation changes of genes HSP70, HSP90, heat shock factor 1 (HSF1), heat shock RNA 1 (HSR1), and eukaryotic translation elongation factor 1 alpha (eEF1a) were investigated with methylation-specific real-time quantitative polymerase chain reaction analysis. Results: The eEF1a was significantly more hypermethylated in Group 1. In Group 2, HSP70, HSP90 HSF1, HSR1, and eEF1a were significantly hypomethylated compared to Group 1 and Group 3 (for all genes p<0.001). The HSF1 hypomethylation was negatively correlated with MMSE and positively correlated with depression scores (p=0.03 and p=0.013, respectively). The correlation of eEF1a with MMSE and depression was the opposite of HSF1 (p<0.001 and p=0.013, respectively). Conclusion: Cell line and autopsy studies indicate that eEF1a hypermethylation might be one of the main molecules triggering alpha-synuclein aggregation in the pathogenesis of PD. Therefore, eEF1a may be a molecule that can be used as a peripheral biomarker. The findings supported this idea as it was more hypermethylated in PD patients than in controls, whereas its negative regulator HSF1 was hypomethylated and correlated with the clinic. Furthermore, the worsening of cognitive functions and depression in PD patients may affect methylation levels of chaperone genes in the peripheral blood. © 2024 by the Turkish Neurological Society.Öğe Possible bradykinesia occurrence in lymphocyte division in Parkinson's disease(Ondokuz Mayis Universitesi, 2024) Inalkac Gemici Y.; Tasci I.; Dundar M.; Ozgen N.; Gozde Gozukara H.; Koc A.Lymphocytes have dopamine receptors, and low dopamine levels increase receptor synthesis. Lymphocytes may move slower in Parkinson's, which is characterized by low dopamine levels. We hypothesized that longer telomeres would indicate less lymphocyte division. We investigated whether leukocyte telomere length (LTL) is different in naïve Parkinson’s disease (PD) patients and whether telomere length has clinical significance in determining telomere length in naïve Parkinson's patients. Naïve patients diagnosed with PD were included in this study. 29 naïve PD patients and 15 controls were included in the study. Subgroup analyses were performed according to MMSE and depression scores of PD patients. LTL was measured by RT-qPCR. Differences in LTL between the groups were examined. Clinical and demographic findings and LTL were examined and correlated using appropriate statistical methods. Forty-four participants meeting the inclusion criteria were included in the study. LTL was significantly longer in PD patients than in the control group (p = 0.043) and was positively correlated with clinical worsening of the disease. According to the Analysis of Moment Structures, evaluation total MMSE was 1.82, UPDRS was -1.53, and depression score was -.31 negatively correlated with telomere. LTL was found to be longer in naïve PD patients than in controls. Without other factors that could affect telomere; these findings support the hypothesis that leukocyte division could be slower in PD than the control group at the same age. Additional studies are needed on this subject. Additionally, a longer TL could be a marker for a better clinical course in PD. © 2024 Ondokuz Mayis Universitesi. All rights reserved.Öğe tRNA Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux(NLM (Medline), 2020) Uluisik I.; ? Karakaya H.; Koc A.Boric acid is essential for plants and has many vital roles in animals and microorganisms. However, its high doses are toxic to all organisms. We previously screened yeast deletion collections to identify boric acid-resistant and susceptible mutants to identify genes that play a role in boron tolerance. Here, we analyzed boron resistant mutants (elpl?, elp3?, elp6?, ncs2?, ncs6? and ktil2?) for their abilities to modulate the general amino acid control system (GAAC) and to induce boron efflux pump ATR1. The mutants analyzed in this study lack the genes that play roles in tRNA Wobble base modifications. We found that all of the boron resistant mutants activated Gcn4-dependent reporter gene activity and increased the transcript level of the ATR1 gene. Additionally, boron resistant cells accumulated less boric acid in their cytoplasm compared to the wild type cells upon boron exposure. Thus, our findings suggested that loss of wobble base modifications in tRNA leads to GAAC activation and ATR1 induction, which in turn reduced intracellular boron levels and caused boron resistance.
