TRIM21 drives intervertebral disc degeneration induced by oxidative stress via mediating HIF-1α degradation
| Autor: | Changwei Li, Jiancheng Zheng, Leilei Chang, Xingkai Zhang, Lianfu Deng, Xiaogang Bao |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Nucleus Pulposus Adolescent Biophysics Intervertebral Disc Degeneration Degeneration (medical) Oxidative phosphorylation medicine.disease_cause Biochemistry Rats Sprague-Dawley Young Adult 03 medical and health sciences 0302 clinical medicine Ubiquitin Downregulation and upregulation medicine Animals Humans Molecular Biology Cells Cultured Aged biology Chemistry Intervertebral disc Hydrogen Peroxide Cell Biology Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit Ubiquitin ligase Cell biology Oxidative Stress 030104 developmental biology medicine.anatomical_structure Ribonucleoproteins 030220 oncology & carcinogenesis Disc degeneration biology.protein Female Oxidative stress |
| Zdroj: | Biochemical and Biophysical Research Communications. 555:46-53 |
| ISSN: | 0006-291X |
| Popis: | The onset and progression of intervertebral disc degeneration (IVDD) is strictly associated with oxidative stress. TRIM21 (Tripartite motif-containing protein 21), a ubiquitin E3 ligase, has been shown to play an essential role in liver redox homeostasis; however, whether TRIM21 is involved in IVDD, especially in oxidative stress-induced IVDD, is unknown. Here, we reported that TRIM21 was upregulated in nucleus pulposus (NPs) with increasing severity of IVDD, and that oxidative stress was a stimulator of TRIM21 expression. Furthermore, we found that TRIM21 deficiency significantly protected NP cells from degeneration induced by oxidative stress as well as ameliorated disc degeneration in aged mice. Mechanistically, TRIM21 facilitated NP cells degeneration induced by oxidative stress via HIF-1α. TRIM21 could physically interact with HIF-1α and facilitated its degradation via its ubiquitylating activity. Taken together, these findings revealed that TRIM21 drived IVDD induced by oxidative stress by increasing HIF-1α degradation. These findings implicates the potential of TRIM21 as a therapeutic target in IVDD, especially in oxidative stress-induced IVDD. |
| Databáze: | OpenAIRE |
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