The H2S-Nrf2-Antioxidant Proteins Axis Protects Renal Tubular Epithelial Cells of the Native Hibernator Syrian Hamster from Reoxygenation-Induced Cell Death

• Published in: Biology (Basel, Switzerland) Switzerland), 2019-09, Vol.8 (4), p.74
• Main Authors: Eleftheriadis, Theodoros, Pissas, Georgios, Nikolaou, Evdokia, Liakopoulos, Vassilios, Stefanidis, Ioannis
• Format: Article
• Language: English
• Subjects: 3-Mercaptopyruvate sulfurtransferase; Anoxia; Antioxidants; Apoptosis; Biological products; Biotechnology; Blood; Body temperature; Cell culture; Cell death; Cystathionine b-synthase; Cystathionine g-lyase; Cytotoxicity; Enzymes; Epithelial cells; Experiments; Ferritin; Glutathione reductase; h2s; Hibernation; Hydrogen sulfide; Ischemia; ischemia-reperfusion; Kidneys; Lipid peroxidation; Methylene blue; Monoclonal antibodies; nrf2; oxidative stress; Polyclonal antibodies; Proteins; Reactive oxygen species; Reperfusion; Sulfurtransferase; Superoxide dismutase; Western blotting
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology8040074

During hibernation, repeated cycles of ischemia-reperfusion (I-R) leave vital organs without injury. Studying this phenomenon may reveal pathways applicable to improving outcomes in I-R injury-induced human diseases. We evaluated whether the H S-nuclear factor erythroid 2-like 2 (Nrf2)-antioxidant proteins axis protects renal proximal tubular epithelial cells (RPTECs) of the native hibernator, the Syrian hamster, from reperfusion-induced cell death. To imitate I-R, the hamsters', and control mice's RPTECs were subjected to warm anoxia, washed, and then subjected to reoxygenation in fresh culture medium. Whenever required, the H S-producing enzymes inhibitor aminooxyacetate or the lipid peroxidation inhibitor α-tocopherol were used. A handmade H S detection methylene blue assay, a reactive oxygen species (ROS) detection kit, a LDH release cytotoxicity assay kit, and western blotting were used. Reoxygenation upregulated the H S-producing enzymes cystathionine beta-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase in the hamster, but not in mouse RPTECs. As a result, H S production increased only in the hamster RPTECs under reoxygenation conditions. Nrf2 expression followed the alterations of H S production leading to an enhanced level of the antioxidant enzymes superoxide dismutase 3 and glutathione reductase, and anti-ferroptotic proteins ferritin H and cystine-glutamate antiporter. The upregulated antioxidant enzymes and anti-ferroptotic proteins controlled ROS production and rescued hamster RPTECs from reoxygenation-induced, lipid peroxidation-mediated cell death. In conclusion, in RPTECs of the native hibernator Syrian hamster, reoxygenation activates the H2S-Nrf2-antioxidant proteins axis, which rescues cells from reoxygenation-induced cell death. Further studies may reveal that the therapeutic activation of this axis in non-hibernating species, including humans, may be beneficial in I-R injury-induced diseases.