Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3-SOD2-mtROS signaling
© 2024 Federation of European Biochemical Societies..
Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:291 |
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| Enthalten in: |
The FEBS journal - 291(2024), 7 vom: 15. Apr., Seite 1575-1592 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xie, Shiying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/febs.17057 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367338726 |
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| 245 | 1 | 0 | |a Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3-SOD2-mtROS signaling |
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| 520 | |a © 2024 Federation of European Biochemical Societies. | ||
| 520 | |a Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a acute kidney injury | |
| 650 | 4 | |a ferroptosis | |
| 650 | 4 | |a ischemia reperfusion | |
| 650 | 4 | |a site 1 protease | |
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| 700 | 1 | |a Liu, Sirui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qinglan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Tiantian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Wei-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Cheng |e verfasserin |4 aut | |
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