Next Article in Journal
Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
Previous Article in Journal
Effects of Pulsed Electric Field on the Cell Wall and Infection Activity of Rhizoctonia solani
Open AccessArticle

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

Department of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Biology 2019, 8(4), 74; https://doi.org/10.3390/biology8040074
Received: 8 September 2019 / Revised: 25 September 2019 / Accepted: 26 September 2019 / Published: 30 September 2019
(This article belongs to the Section Cell Biology)
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 H2S–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 H2S-producing enzymes inhibitor aminooxyacetate or the lipid peroxidation inhibitor α-tocopherol were used. A handmade H2S 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 H2S-producing enzymes cystathionine beta-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase in the hamster, but not in mouse RPTECs. As a result, H2S production increased only in the hamster RPTECs under reoxygenation conditions. Nrf2 expression followed the alterations of H2S 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. View Full-Text
Keywords: hibernation; H2S; Nrf2; oxidative stress; ischemia-reperfusion; cell death hibernation; H2S; Nrf2; oxidative stress; ischemia-reperfusion; cell death
Show Figures

Figure 1

MDPI and ACS Style

Eleftheriadis, T.; Pissas, G.; Nikolaou, E.; Liakopoulos, V.; Stefanidis, I. The H2S–Nrf2–Antioxidant Proteins Axis Protects Renal Tubular Epithelial Cells of the Native Hibernator Syrian Hamster from Reoxygenation-Induced Cell Death. Biology 2019, 8, 74.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop