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Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner
Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin-β is abundantly expressed in the kidneys. However, it is unclear whether salusin-β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335735/ https://www.ncbi.nlm.nih.gov/pubmed/34296310 http://dx.doi.org/10.3892/mmr.2021.12313 |
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author | Wang, Wen-Juan Jiang, Xia Gao, Chang-Chun Chen, Zhi-Wei |
author_facet | Wang, Wen-Juan Jiang, Xia Gao, Chang-Chun Chen, Zhi-Wei |
author_sort | Wang, Wen-Juan |
collection | PubMed |
description | Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin-β is abundantly expressed in the kidneys. However, it is unclear whether salusin-β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin-β in a dose- and time-dependent manner. Genetic knockdown of salusin-β retarded, whereas overexpression of salusin-β aggravated, HG-triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK-2 cells. Mechanistically, salusin-β inactivated nuclear factor erythroid-derived 2-like 2 (Nrf-2) signaling, thus contributing to HG-induced ferroptosis-related changes in HK-2 cells. Notably, the protein expression of salusin-β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin-1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin-β in HK-2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin-β and ferroptosis primes renal tubular cells for injury in diabetes. |
format | Online Article Text |
id | pubmed-8335735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-83357352021-08-24 Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner Wang, Wen-Juan Jiang, Xia Gao, Chang-Chun Chen, Zhi-Wei Mol Med Rep Articles Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin-β is abundantly expressed in the kidneys. However, it is unclear whether salusin-β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin-β in a dose- and time-dependent manner. Genetic knockdown of salusin-β retarded, whereas overexpression of salusin-β aggravated, HG-triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK-2 cells. Mechanistically, salusin-β inactivated nuclear factor erythroid-derived 2-like 2 (Nrf-2) signaling, thus contributing to HG-induced ferroptosis-related changes in HK-2 cells. Notably, the protein expression of salusin-β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin-1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin-β in HK-2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin-β and ferroptosis primes renal tubular cells for injury in diabetes. D.A. Spandidos 2021-09 2021-07-22 /pmc/articles/PMC8335735/ /pubmed/34296310 http://dx.doi.org/10.3892/mmr.2021.12313 Text en Copyright: © Wang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wang, Wen-Juan Jiang, Xia Gao, Chang-Chun Chen, Zhi-Wei Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title | Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title_full | Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title_fullStr | Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title_full_unstemmed | Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title_short | Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner |
title_sort | salusin-β participates in high glucose-induced hk-2 cell ferroptosis in a nrf-2-dependent manner |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335735/ https://www.ncbi.nlm.nih.gov/pubmed/34296310 http://dx.doi.org/10.3892/mmr.2021.12313 |
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