A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress
Copyright © 2024 Elsevier B.V. All rights reserved..
Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
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| Enthalten in: |
International immunopharmacology - 131(2024) vom: 20. Apr., Seite 111861 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Guo-Dong [VerfasserIn] |
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| Links: |
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| Themen: |
362O9ITL9D |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111861 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369743539 |
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| 245 | 1 | 2 | |a A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress |
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| 520 | |a Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Li-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shi-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Rong-Quan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yu-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ming-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tian-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Bao-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lei |e verfasserin |4 aut | |
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