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ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway
Ferroptosis participates in the occurrence and development of neurological disorders. Modulating ferroptosis may have therapeutic potential in nervous system diseases. Therefore, TMTbased proteomic analysis in HT-22 cells was performed to identify erastin–induced differentially expressed proteins. T...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252295/ https://www.ncbi.nlm.nih.gov/pubmed/37298147 http://dx.doi.org/10.3390/ijms24119199 |
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author | Guo, Shihui Zhong, Aiying Zhang, Dongxu Gao, Jiang Ni, Yingdong Zhao, Ruqian Ma, Wenqiang |
author_facet | Guo, Shihui Zhong, Aiying Zhang, Dongxu Gao, Jiang Ni, Yingdong Zhao, Ruqian Ma, Wenqiang |
author_sort | Guo, Shihui |
collection | PubMed |
description | Ferroptosis participates in the occurrence and development of neurological disorders. Modulating ferroptosis may have therapeutic potential in nervous system diseases. Therefore, TMTbased proteomic analysis in HT-22 cells was performed to identify erastin–induced differentially expressed proteins. The calcium-transporting ATP2B3 (ATP2B3) was screened as a target protein. ATP2B3 knockdown markedly alleviated the erastin–induced decrease in cell viability and elevated ROS (p < 0.01) and reversed the up-regulation of oxidative stress-related proteins polyubiquitin-binding protein p62 (P62), nuclear factor erythroid 2-related factor2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase-1 (NQO1) protein expression (p < 0.05 or p < 0.01) and the down−regulation of Kelch-like ECH-associated protein 1(KEAP1) protein expression (p < 0.01). Moreover, NRF2 knockdown, P62 inhibition, or KEAP1 overexpression rescued the erastin–induced decrease in cell viability (p < 0.05) and increase in ROS production (p < 0.01) in HT-22 cells, while simultaneous overexpression of NRF2 and P62 and knockdown of KEAP1 partially offset the relief effect of ATP2B3 inhibition. In addition, knockdown of ATP2B3, NRF2, and P62 and overexpression of KEAP1 significantly down-regulated erastin–induced high expression of the HO-1 protein, while HO-1 overexpression reversed the alleviating effects of ATP2B3 inhibition on the erastin–induced decrease in cell viability (p < 0.01) and increase in ROS production (p < 0.01) in HT-22 cells. Taken together, ATP2B3 inhibition mediates the alleviation of erastin–induced ferroptosis in HT-22 cells through the P62–KEAP1–NRF2–HO-1 pathway. |
format | Online Article Text |
id | pubmed-10252295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102522952023-06-10 ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway Guo, Shihui Zhong, Aiying Zhang, Dongxu Gao, Jiang Ni, Yingdong Zhao, Ruqian Ma, Wenqiang Int J Mol Sci Article Ferroptosis participates in the occurrence and development of neurological disorders. Modulating ferroptosis may have therapeutic potential in nervous system diseases. Therefore, TMTbased proteomic analysis in HT-22 cells was performed to identify erastin–induced differentially expressed proteins. The calcium-transporting ATP2B3 (ATP2B3) was screened as a target protein. ATP2B3 knockdown markedly alleviated the erastin–induced decrease in cell viability and elevated ROS (p < 0.01) and reversed the up-regulation of oxidative stress-related proteins polyubiquitin-binding protein p62 (P62), nuclear factor erythroid 2-related factor2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase-1 (NQO1) protein expression (p < 0.05 or p < 0.01) and the down−regulation of Kelch-like ECH-associated protein 1(KEAP1) protein expression (p < 0.01). Moreover, NRF2 knockdown, P62 inhibition, or KEAP1 overexpression rescued the erastin–induced decrease in cell viability (p < 0.05) and increase in ROS production (p < 0.01) in HT-22 cells, while simultaneous overexpression of NRF2 and P62 and knockdown of KEAP1 partially offset the relief effect of ATP2B3 inhibition. In addition, knockdown of ATP2B3, NRF2, and P62 and overexpression of KEAP1 significantly down-regulated erastin–induced high expression of the HO-1 protein, while HO-1 overexpression reversed the alleviating effects of ATP2B3 inhibition on the erastin–induced decrease in cell viability (p < 0.01) and increase in ROS production (p < 0.01) in HT-22 cells. Taken together, ATP2B3 inhibition mediates the alleviation of erastin–induced ferroptosis in HT-22 cells through the P62–KEAP1–NRF2–HO-1 pathway. MDPI 2023-05-24 /pmc/articles/PMC10252295/ /pubmed/37298147 http://dx.doi.org/10.3390/ijms24119199 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Guo, Shihui Zhong, Aiying Zhang, Dongxu Gao, Jiang Ni, Yingdong Zhao, Ruqian Ma, Wenqiang ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title | ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title_full | ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title_fullStr | ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title_full_unstemmed | ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title_short | ATP2B3 Inhibition Alleviates Erastin–Induced Ferroptosis in HT-22 Cells through the P62–KEAP1–NRF2–HO-1 Pathway |
title_sort | atp2b3 inhibition alleviates erastin–induced ferroptosis in ht-22 cells through the p62–keap1–nrf2–ho-1 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252295/ https://www.ncbi.nlm.nih.gov/pubmed/37298147 http://dx.doi.org/10.3390/ijms24119199 |
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