Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-β-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:170 |
|---|---|
| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 170(2024) vom: 02. Jan., Seite 116042 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liao, Jing [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 10.01.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.biopha.2023.116042 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366090143 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366090143 | ||
| 003 | DE-627 | ||
| 005 | 20240114233504.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.biopha.2023.116042 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1255.xml |
| 035 | |a (DE-627)NLM366090143 | ||
| 035 | |a (NLM)38118351 | ||
| 035 | |a (PII)S0753-3322(23)01840-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liao, Jing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.01.2024 | ||
| 500 | |a Date Revised 10.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved. | ||
| 520 | |a Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-β-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NOX1 and NOX4 | |
| 650 | 4 | |a Retinal ganglion cells | |
| 650 | 4 | |a Retinal ischemia-reperfusion | |
| 650 | 4 | |a Setanaxib | |
| 650 | 7 | |a setanaxib |2 NLM | |
| 650 | 7 | |a 45II35329V |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a NADPH Oxidase 4 |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a NOX1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a NADPH Oxidase 1 |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a NOX4 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 700 | 1 | |a Lai, Zhaoguang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Guangyi |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Jiali |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Yuanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yaguang |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Qiaochu |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Haibin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yantao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Fan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie |d 1984 |g 170(2024) vom: 02. Jan., Seite 116042 |w (DE-627)NLM012645591 |x 1950-6007 |7 nnns |
| 773 | 1 | 8 | |g volume:170 |g year:2024 |g day:02 |g month:01 |g pages:116042 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.biopha.2023.116042 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 170 |j 2024 |b 02 |c 01 |h 116042 | ||