دورية أكاديمية
TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the mTOR/S6KP70 Axis.
| العنوان: | TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the mTOR/S6KP70 Axis. |
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| المؤلفون: | Tan QL; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Zhang MX; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Yao DH; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Yan Y; Department of Endocrinology, The Third People's Hospital of Datong, Datong, PR China., Yang XF; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Qin ZH; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Gong Y; Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China., Meng Q; The Third Department of Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, PR China. |
| المصدر: | Nutrition and cancer [Nutr Cancer] 2023; Vol. 75 (6), pp. 1464-1472. Date of Electronic Publication: 2023 May 04. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Routledge Country of Publication: United States NLM ID: 7905040 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-7914 (Electronic) Linking ISSN: 01635581 NLM ISO Abbreviation: Nutr Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Philadelphia : Routledge Original Publication: Philadelphia, Franklin Institute Press. |
| مواضيع طبية MeSH: | Ferroptosis*, Humans ; Apoptosis ; Reactive Oxygen Species/metabolism ; Adenine/pharmacology ; Phosphoric Monoester Hydrolases/metabolism ; Apoptosis Regulatory Proteins/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Glutathione/metabolism ; Epithelial Cells/metabolism ; Glycolysis ; Iron |
| مستخلص: | TP53-induced glycolysis and apoptosis regulator (TIGAR) acts as a switch for nephropathy, but its underlying mechanism is still unclear. The purpose of this study was to explore the potential biological significance and underlying mechanism of TIGAR in modulating adenine-induced ferroptosis in human proximal tubular epithelial (HK-2) cells. HK-2 cells under- or overexpressing TIGAR were challenged with adenine to induce ferroptosis. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were assayed. Expression of ferroptosis-associated solute carrier family seven-member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) at the level of mRNA and protein were measured by quantitative real-time-PCR and western blotting. The phosphorylation levels of proteins in the mTOR/S6KP70 pathway were determined by western blotting. Adenine overload triggered ferroptosis in HK-2 cells, as evidenced by reduced levels of GSH, SLC7A11, and GPX4, and increased levels of iron, MDA, and ROS. TIGAR overexpression repressed adenine-induced ferroptosis and induced mTOR/S6KP70 signaling. Inhibitors of mTOR and S6KP70 weakened the ability of TIGAR to inhibit adenine-induced ferroptosis. TIGAR inhibits adenine-induced ferroptosis in human proximal tubular epithelial cells by activating the mTOR/S6KP70 signaling pathway. Therefore, activating the TIGAR/mTOR/S6KP70 axis may be a treatment for crystal nephropathies. |
| المشرفين على المادة: | 0 (Reactive Oxygen Species) JAC85A2161 (Adenine) EC 3.1.3.2 (Phosphoric Monoester Hydrolases) 0 (Apoptosis Regulatory Proteins) EC 2.7.11.1 (TOR Serine-Threonine Kinases) GAN16C9B8O (Glutathione) E1UOL152H7 (Iron) |
| تواريخ الأحداث: | Date Created: 20230504 Date Completed: 20230621 Latest Revision: 20230621 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1080/01635581.2023.2203353 |
| PMID: | 37140263 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1532-7914 |
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| DOI: | 10.1080/01635581.2023.2203353 |