Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells
| Autor: | Haruna Nagase, Yasuhiro Katagiri, Kentaro Oh-hashi, Herbert M. Geller, Yoko Hirata |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Biomolecules, Vol 10, Iss 1, p 92 (2020) |
| Druh dokumentu: | article |
| ISSN: | 2218-273X 10010092 |
| DOI: | 10.3390/biom10010092 |
| Popis: | Sulfation is a common modification of extracellular glycans, tyrosine residues on proteins, and steroid hormones, and is important in a wide variety of signaling pathways. We investigated the role of sulfation on endogenous oxidative stress, such as glutamate-induced oxytosis and erastin-induced ferroptosis, using mouse hippocampal HT22 cells. Sodium chlorate competitively inhibits the formation of 3′-phosphoadenosine 5′-phosphosulfate, the high energy sulfate donor in cellular sulfation reactions. The treatment of HT22 cells with sodium chlorate decreased sulfation of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Sodium chlorate and β-d-xyloside, which prevents proteoglycan glycosaminoglycan chain attachment, exacerbated both glutamate- and erastin-induced cell death, suggesting that extracellular matrix influenced oxytosis and ferroptosis. Moreover, sodium chlorate enhanced the generation of reactive oxygen species and influx of extracellular Ca2+ in the process of oxytosis and ferroptosis. Interestingly, sodium chlorate did not affect antioxidant glutathione levels. Western blot analysis revealed that sodium chlorate enhanced erastin-induced c-Jun N-terminal kinase phosphorylation, which is preferentially activated by cell stress-inducing signals. Collectively, our findings indicate that sulfation is an important modification for neuroprotection against oxytosis and ferroptosis in neuronal hippocampal cells. |
| Databáze: | Directory of Open Access Journals |
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