Cell Death Patterns Due to Warm Ischemia or Reperfusion in Renal Tubular Epithelial Cells Originating from Human, Mouse, or the Native Hibernator Hamster

Eleftheriadis, Theodoros; Pissas, Georgios; Antoniadi, Georgia; Liakopoulos, Vassilios; Stefanidis, Ioannis

doi:10.3390/biology7040048

Cited by 30 publications

(45 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This pathway, albeit not well-studied in hibernators, defends against ROS disruption of cell integrity [18]. We evaluated the H2S-Nrf2-antioxidant proteins axis only under reoxygenation conditions, since according to a previous study of our laboratory [13], both in mouse and hamster RPTECs, ROS production increases under reoxygenation, when oxygen is available, and not under anoxia. Thus, this axis could play a protective role only under reoxygenation.…”

Section: Discussionmentioning

confidence: 99%

“…Next, danger associated molecular patterns are released by the necrotic cells and activate the immune system [32], resulting in a secondary wave of necroptotic cell death. Importantly, cultured Syrian hamster RPTECs resist warm anoxia-reoxygenation injury, whereas mouse RPTECs die from apoptosis during warm anoxia and ferroptosis during reoxygenation [13]. To evaluate the role of the H 2 S-Nrf2-anti-ferroptotic proteins axis, activated by reoxygenation, in hamster RPTECs, we assessed the impact of the H 2 S-producing enzymes inhibitor AOAA and the lipid-peroxidation inhibitor α-tocopherol on cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, one should keep in mind that in I-R injury, cell death occurs not only during the reoxygenation period but also during the preceding anoxia. For example, mouse RPTECs die through apoptosis during warm anoxia and ferroptosis during reoxygenation [13]. Thus, a combination of substances that inhibit different types of cell death, for instance, apoptosis and ferroptosis, may be required for an optimum effect.…”

Section: Discussionmentioning

confidence: 99%

“…The periods of anoxia and reoxygenation were selected in accordance with a previous study of our laboratory, upon which it was shown that primary Syrian hamster RPTECs are extremely resistant to both anoxia and reoxygenation, whereas primary mouse RPTECs decline considerably after 48 h of anoxia or 4 h of reoxygenation [13]. All the experiments were repeated nine times.…”

Section: Cells and Culture Conditionsmentioning

confidence: 99%

“…Syrian hamster renal proximal tubular epithelial cells (RPTECs) resist warm anoxia-reoxygenation injury as well. On the contrary, mouse (Mus musculus) RPTECs die from apoptosis during warm anoxia and ferroptosis during reoxygenation [13]. Yet, the pathways involved in the protection of hamster RPTECs from the oxidative stress and the subsequent ferroptosis during reoxygenation are not well-understood.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Eleftheriadis

Pissas

Nikolaou

et al. 2019

Biology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cells and Culture Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Eleftheriadis

Pissas

Nikolaou

et al. 2019

Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Role of ferroptosis in gastrointestinal tumors: From mechanisms to therapies

Zhou

Deng

et al. 2022

Cell Biology International

View full text Add to dashboard Cite

Ferroptosis is an iron‐dependent nonapoptotic regulated cell death, which is mainly caused by an abnormal increase in lipid oxygen free radicals and an imbalance in redox homeostasis. Recently, ferroptosis has been shown to have implications in various gastrointestinal cancers, such as gastric carcinoma, hepatocellular carcinoma, and pancreatic cancer. This review summarises the latest research on ferroptosis, its mechanism of action, and its role in the progression of different gastrointestinal tumors to provide more information regarding the prevention and treatment of these tumors.

show abstract

Integrated transcriptomics and metabolomics reveal protective effects on heart of hibernating Daurian ground squirrels

Yang,

Hao,

et al. 2023

Journal Cellular Physiology

View full text Add to dashboard Cite

Hibernating mammals are natural models of resistance to ischemia, hypoxia‐reperfusion injury, and hypothermia. Daurian ground squirrels (spermophilus dauricus) can adapt to endure multiple torpor‐arousal cycles without sustaining cardiac damage. However, the molecular regulatory mechanisms that underlie this adaptive response are not yet fully understood. This study investigates morphological, functional, genetic, and metabolic changes that occur in the heart of ground squirrels in three groups: summer active (SA), late torpor (LT), and interbout arousal (IBA). Morphological and functional changes in the heart were measured using hematoxylin‐eosin (HE) staining, Masson staining, echocardiography, and enzyme‐linked immunosorbent assay (ELISA). Results showed significant changes in cardiac function in the LT group as compared with SA or IBA groups, but no irreversible damage occurred. To understand the molecular mechanisms underlying these phenotypic changes, transcriptomic and metabolomic analyses were conducted to assess differential changes in gene expression and metabolite levels in the three groups of ground squirrels, with a focus on GO and KEGG pathway analysis. Transcriptomic analysis showed that differentially expressed genes were involved in the remodeling of cytoskeletal proteins, reduction in protein synthesis, and downregulation of the ubiquitin‐proteasome pathway during hibernation (including LT and IBA groups), as compared with the SA group. Metabolomic analysis revealed increased free amino acids, activation of the glutathione antioxidant system, altered cardiac fatty acid metabolic preferences, and enhanced pentose phosphate pathway activity during hibernation as compared with the SA group. Combining the transcriptomic and metabolomic data, active mitochondrial oxidative phosphorylation and creatine‐phosphocreatine energy shuttle systems were observed, as well as inhibition of ferroptosis signaling pathways during hibernation as compared with the SA group. In conclusion, these results provide new insights into cardio‐protection in hibernators from the perspective of gene and metabolite changes and deepen our understanding of adaptive cardio‐protection mechanisms in mammalian hibernators.

show abstract

Cell Death Patterns Due to Warm Ischemia or Reperfusion in Renal Tubular Epithelial Cells Originating from Human, Mouse, or the Native Hibernator Hamster

Cited by 30 publications

References 47 publications

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

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

Role of ferroptosis in gastrointestinal tumors: From mechanisms to therapies

Integrated transcriptomics and metabolomics reveal protective effects on heart of hibernating Daurian ground squirrels

Contact Info

Product

Resources

About