Reduced Sulfation Enhanced Oxytosis and Ferroptosis in Mouse Hippocampal HT22 Cells.

Biomolecules (2020-01-16)
Haruna Nagase, Yasuhiro Katagiri, Kentaro Oh-Hashi, Herbert M Geller, Yoko Hirata
RESUMEN

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.

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Sigma-Aldrich
Phthaldialdehyde, suitable for HPLC fluorimetric detection of amino acids, ≥99% (HPLC), powder
Sigma-Aldrich
Erastin, ≥98% (HPLC)
Sigma-Aldrich
4-Methylumbelliferyl-β-D-xylopyranoside, β-xylosidase substrate