Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells
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 fer...
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MDPI AG
2020-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/1/92 |
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| author | Haruna Nagase Yasuhiro Katagiri Kentaro Oh-hashi Herbert M. Geller Yoko Hirata |
| author_facet | Haruna Nagase Yasuhiro Katagiri Kentaro Oh-hashi Herbert M. Geller Yoko Hirata |
| author_sort | Haruna Nagase |
| collection | DOAJ |
| description | 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-<span style="font-variant: small-caps;">d</span>-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 Ca<sup>2+</sup> 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. |
| first_indexed | 2024-12-11T23:57:30Z |
| format | Article |
| id | doaj.art-e3efc23ce100464a88a1b7fcf63ab028 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-11T23:57:30Z |
| publishDate | 2020-01-01 |
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| series | Biomolecules |
| spelling | doaj.art-e3efc23ce100464a88a1b7fcf63ab0282022-12-22T00:45:19ZengMDPI AGBiomolecules2218-273X2020-01-011019210.3390/biom10010092biom10010092Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 CellsHaruna Nagase0Yasuhiro Katagiri1Kentaro Oh-hashi2Herbert M. Geller3Yoko Hirata4United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido, Gifu 501-1193, JapanLaboratory of Developmental Neurobiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USAUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido, Gifu 501-1193, JapanLaboratory of Developmental Neurobiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USAUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido, Gifu 501-1193, JapanSulfation 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-<span style="font-variant: small-caps;">d</span>-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 Ca<sup>2+</sup> 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.https://www.mdpi.com/2218-273X/10/1/92oxidative stressoxytosisferroptosisproteoglycanssodium chloratesulfation |
| spellingShingle | Haruna Nagase Yasuhiro Katagiri Kentaro Oh-hashi Herbert M. Geller Yoko Hirata Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells Biomolecules oxidative stress oxytosis ferroptosis proteoglycans sodium chlorate sulfation |
| title | Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells |
| title_full | Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells |
| title_fullStr | Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells |
| title_full_unstemmed | Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells |
| title_short | Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells |
| title_sort | reduced sulfation enhanced oxytosis and ferroptosis in mouse hippocampal ht22 cells |
| topic | oxidative stress oxytosis ferroptosis proteoglycans sodium chlorate sulfation |
| url | https://www.mdpi.com/2218-273X/10/1/92 |
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