Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 13Citation - Scopus: 15Prevention of Cisplatin-Induced Nephrotoxicity by Kidney-Targeted siRNA Delivery(Elsevier, 2022-11) Aydin, Erkin; Cebeci, Aysun; Lekesizcan, AycaCisplatin is a potent and widely used chemotherapy agent, however, nephrotoxicity limits its use. Many patients need to pause or withdraw from chemotherapy to prevent acute kidney injury. To prevent cisplatin damage, we designed chitosan/siRNA nanoparticleswhich are nontoxic and are readily taken up by HEK293 cells. The nanoparticles contained siRNA against cationic membrane transport (OCT1&2) and apoptosis related proteins (p53, PKC8, and gamma GT). In mice treated with cisplatin, serum creatinine levels increased from 15 to 88 mg/dL and blood urea nitrogen levels increased from 0.25 to 1.7 mg/dL, however, siRNA nanoparticles significantly limited these levels to 30 mg/dL and 0.55 mg/dL, respectively. Western and IHC analyses showed lower p53, PKC8, and gamma GT expressions in siRNA treated mice. Histomorphological evaluation revealed high-level protection of kidney proximal tubules from cisplatin damage. Protein expressions and extent of kidney protection were directly correlated with number of siRNA applications. Our results suggest that this novel approach for kidney -targeted delivery of select siRNAs may represent a promising therapy for preventing cisplatin-induced nephro-toxicity. Furthermore, this or other similarly sized nanocarriers could potentially be utilized to passively target kidneys for diagnostic, protective, or treatment purposes.Article Citation - WoS: 35Citation - Scopus: 37Glucose-Dependent Anaplerosis in Cancer Cells Is Required for Cellular Redox Balance in the Absence of Glutamine(Nature Portfolio, 2016-09-08) Cetinbas, Naniye Malli; Sudderth, Jessica; Harris, Robert C.; Cebeci, Aysun; Negri, Gian L.; Yilmaz, Oemer H.; Sorensen, Poul H.; Yllmaz, Ömer H.Cancer cells have altered metabolism compared to normal cells, including dependence on glutamine (GLN) for survival, known as GLN addiction. However, some cancer cell lines do not require GLN for survival and the basis for this discrepancy is not well understood. GLN is a precursor for antioxidants such as glutathione (GSH) and NADPH, and GLN deprivation is therefore predicted to deplete antioxidants and increase reactive oxygen species (ROS). Using diverse human cancer cell lines we show that this occurs only in cells that rely on GLN for survival. Thus, the preference for GLN as a dominant antioxidant source defines GLN addiction. We show that despite increased glucose uptake, GLN addicted cells do not metabolize glucose via the TCA cycle when GLN is depleted, as revealed by C-13-glucose labeling. In contrast, GLN independent cells can compensate by diverting glucose-derived pyruvate into the TCA cycle. GLN addicted cells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GLN starvation-induced ROS and cell death. Finally, we show that combining GLN starvation with pro-oxidants selectively kills GLN addicted cells. These data highlight a major role for GLN in maintaining redox balance in cancer cells that lack glucose-dependent anaplerosis.