Hydrogen sulfide improves endothelial barrier function by modulating the ubiquitination degradation of KLF4 through TRAF7 S-sulfhydration in diabetic aorta
Copyright © 2024 Elsevier Inc. All rights reserved..
Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein. However, the role of S-sulfhydration on endothelial barrier integrity remains to be comprehensively elucidated. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates endothelial integrity and its underlying mechanism. In this study, we observed that protein S-sulfhydration was reduced in the endothelium during diabetes and TRAF7 was the main target. Overexpression of TRAF7-Cys327 mutant could mitigate the endothelial barrier damage by weakening TRAF7 interaction with KLF4 and reducing ubiquitination degradation of KLF4. In conclusion, our research demonstrates that H2S plays a pivotal role in regulating S-sulfhydration of TRAF7 at Cys327. This regulation effectively inhibits the ubiquitin-mediated degradation of KLF4, resulting in an upregulation of VE-cadherin levels. This molecular mechanism contributes to the prevention of endothelial barrier damage.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:216 |
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| Enthalten in: |
Free radical biology & medicine - 216(2024) vom: 11. Apr., Seite 118-138 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Qianzhu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.freeradbiomed.2024.02.024 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369693450 |
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| 245 | 1 | 0 | |a Hydrogen sulfide improves endothelial barrier function by modulating the ubiquitination degradation of KLF4 through TRAF7 S-sulfhydration in diabetic aorta |
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| 520 | |a Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein. However, the role of S-sulfhydration on endothelial barrier integrity remains to be comprehensively elucidated. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates endothelial integrity and its underlying mechanism. In this study, we observed that protein S-sulfhydration was reduced in the endothelium during diabetes and TRAF7 was the main target. Overexpression of TRAF7-Cys327 mutant could mitigate the endothelial barrier damage by weakening TRAF7 interaction with KLF4 and reducing ubiquitination degradation of KLF4. In conclusion, our research demonstrates that H2S plays a pivotal role in regulating S-sulfhydration of TRAF7 at Cys327. This regulation effectively inhibits the ubiquitin-mediated degradation of KLF4, resulting in an upregulation of VE-cadherin levels. This molecular mechanism contributes to the prevention of endothelial barrier damage | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Endothelial permeability | |
| 650 | 4 | |a Hydrogen sulphide (H(2)S) | |
| 650 | 4 | |a Krueppel-like factor 4(KLF4) | |
| 650 | 4 | |a Tumor necrosis factor receptor-associated factor 7 (TRAF7) | |
| 650 | 4 | |a VE-Cadherin | |
| 650 | 7 | |a Hydrogen Sulfide |2 NLM | |
| 650 | 7 | |a YY9FVM7NSN |2 NLM | |
| 650 | 7 | |a Ubiquitin |2 NLM | |
| 700 | 1 | |a Kang, Jiaxin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xueya |e verfasserin |4 aut | |
| 700 | 1 | |a Pang, Kemiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shiwu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Mengyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yajun |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Shiyun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Dechao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Fanghao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weihua |e verfasserin |4 aut | |
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