Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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    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.
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    Oncolytic Myxoma virus Increases Autophagy in Multiple Myeloma
    (2023) Yesilaltay, Alpay; Muz, Dilek; Erdal, Berna; 0000-0003-3375-7926; 0000-0003-3784-5739; 38258554; AEE-3091-2022; HKW-1077-2023
    Objective: Multiple myeloma, which affects plasma cells, is the second most common hematological malignancy. Despite the development of new drugs and treatment protocols, patient survival has not reached the desired level. In this study, we investigated the effects of Myxoma virus (MYXV), an oncolytic virus, on autophagy in myeloma cells. Materials and Methods: We analyzed protein expressions of ATG-5, p62, Beclin-1, LC3B, and the apoptosis marker Bcl-2 as autophagy markers in human U-266 and mouse MOPC-315 myeloma cell lines subjected to different doses of MYXV. In addition, autophagic images of myeloma cells were investigated using transmission electron microscopy (TEM). Results: In the first 24 h, which is the early stage of autophagy, ATG-5 and Beclin-1 expression levels were increased in the U-266 and MOPC315 cell lines in the groups that had received MYXV at a multiplicity of infection of 15. At 48 h, a significant increase was detected in the expression of LC3B, which is a late indicator. Autophagosomes were observed in myeloma cells by TEM. Conclusion: MYXV shows an antimyeloma effect by increasing autophagy in myeloma cells.
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    Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis
    (2021) Yildirim, Derya; Bender, Onur; Karagoz, Zehra Firat; Helvacioglu, Fatma; Bilgic, Mukadder Ayse; Akcay, Ali; Ruzgaresen, Nuket Bavbek; 0000-0002-6026-0045; 34087284
    Aims: Focal segmental glomerulosclerosis (FSGS) is the common cause of chronic renal disease worldwide. Although there are many etiologic factors which have common theme of podocyte injury conclusive etiology is not clearly understood. In this study, we aimed to explore the role of autophagy in the pathogenesis of podocyte injury, which is the key point in disease progression, and the roles of intrarenal microRNAs and the prorenin receptor (PRR) in the 5/6 nephrectomy and adriamycin nephropathy models of FSGS. Main methods: For experimental FSGS model, 5/6 nephrectomy and adriamycin nephropathy models were created and characterized in adult Sprague Dawley rats. Microarray analysis was performed on FSGS and control groups that was confirmed by q-RT-PCR. Beclin1, LC3B, PRR, ATG7 and ATG5 expression were evaluated by western blotting and immunohistochemistry. Also, Beclin1 and PRR expression were measured by ELISA. Glomerular podocyte isolation was performed and autophagic activity was evaluated in podocytes before and after transfection with miRNA mimic and antagonists. Key findings: Glomerular expression of Beclin1, LC3B, PRR, ATG7 and ATG5 were significantly lower in the 5/6 nephrectomy than adriamycin nephropathy group and in both groups lower when compared to control groups. Western blot results were consistent with immunohistochemical data. Electron microscopy revealed signs of impaired autophagy in FSGS. Autophagic activity decreased significantly after miR-214, miR-132 and miR-34c mimics and increased after transfection with antagonists. Significance: These results showed that the role of autophagic activity and decreased expression of PRR in FSGS pathogenesis and miR-34c, miR-132 and miR-214 could be a potential treatment strategy by regulating autophagy.