HO-1 induced autophagy protects against IL-1 β-mediated apoptosis in human nucleus pulposus cells by inhibiting NF-κB
In this study, we investigated the role of heme oxygenase-1 (HO-1) in intervertebral disc degeneration (IDD) by assessing the effects of HO-1 overexpression on IL-1β-induced apoptosis in nucleus pulposus cells (NPCs). Immunohistochemical staining showed HO-1 expression to be lower in NPCs from IDD patients than from patients with lumbar vertebral fractures (LVF). Western blot analysis showed HO-1 and LC3-II/I levels to be lower in NP tissues from IDD patients than from LVF patients, suggesting suppression of autophagy in degenerative intervertebral disc. Consistent with that idea, autophagy was increased in HO-1-overexpressing NPCs while IL-1β-induced apoptosis was reduced. These effects were reversed by treatment with the early autophagy inhibitor 3-methyl adenine, which suggests HO-1-induced autophagy suppresses IL-1β-induced apoptosis in NPCs. HO-1 overexpression promoted autophagy by increasing levels of Beclin-1/PI3KC3 complex. Phospho-P65 levels were lower in HO-1-overexpressing NPCs, suggesting inhibition of NF-κB-mediated apoptosis. Our study thus demonstrates that HO-1 promotes autophagy by enhancing formation of Beclin-1/PI3KC3 complex and suppresses IL-1β-induced apoptosis by inhibiting NF-κB. We suggest that HO-1 is a potential therapeutic target to alleviate IDD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Aging - 12(2020), 3 vom: 04. Feb., Seite 2440-2452 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zou, Luetao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.01.2021 Date Revised 19.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.18632/aging.102753 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306107260 |
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| 245 | 1 | 0 | |a HO-1 induced autophagy protects against IL-1 β-mediated apoptosis in human nucleus pulposus cells by inhibiting NF-κB |
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| 520 | |a In this study, we investigated the role of heme oxygenase-1 (HO-1) in intervertebral disc degeneration (IDD) by assessing the effects of HO-1 overexpression on IL-1β-induced apoptosis in nucleus pulposus cells (NPCs). Immunohistochemical staining showed HO-1 expression to be lower in NPCs from IDD patients than from patients with lumbar vertebral fractures (LVF). Western blot analysis showed HO-1 and LC3-II/I levels to be lower in NP tissues from IDD patients than from LVF patients, suggesting suppression of autophagy in degenerative intervertebral disc. Consistent with that idea, autophagy was increased in HO-1-overexpressing NPCs while IL-1β-induced apoptosis was reduced. These effects were reversed by treatment with the early autophagy inhibitor 3-methyl adenine, which suggests HO-1-induced autophagy suppresses IL-1β-induced apoptosis in NPCs. HO-1 overexpression promoted autophagy by increasing levels of Beclin-1/PI3KC3 complex. Phospho-P65 levels were lower in HO-1-overexpressing NPCs, suggesting inhibition of NF-κB-mediated apoptosis. Our study thus demonstrates that HO-1 promotes autophagy by enhancing formation of Beclin-1/PI3KC3 complex and suppresses IL-1β-induced apoptosis by inhibiting NF-κB. We suggest that HO-1 is a potential therapeutic target to alleviate IDD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Beclin-1/PI3KC3 complex | |
| 650 | 4 | |a Heme oxygenase-1 (HO-1) | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a nucleus pulposus cells (NPCs) | |
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| 700 | 1 | |a Lei, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Jieliang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xulin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Longxi |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhenming |e verfasserin |4 aut | |
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