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Open AccessArticle

Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells

1
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido, Gifu 501-1193, Japan
2
Laboratory of Developmental Neurobiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
3
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 92; https://doi.org/10.3390/biom10010092 (registering DOI)
Received: 8 December 2019 / Revised: 25 December 2019 / Accepted: 4 January 2020 / Published: 6 January 2020
(This article belongs to the Section Biomacromolecules)
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. View Full-Text
Keywords: oxidative stress; oxytosis; ferroptosis; proteoglycans; sodium chlorate; sulfation oxidative stress; oxytosis; ferroptosis; proteoglycans; sodium chlorate; sulfation
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MDPI and ACS Style

Nagase, H.; Katagiri, Y.; Oh-hashi, K.; Geller, H.M.; Hirata, Y. Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells. Biomolecules 2020, 10, 92.

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