The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3
Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the futu...
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Elsevier
2023-06-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723001088 |
| _version_ | 1797830062307803136 |
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| author | Jian Zhu Ruping Sun Kaiqiang Sun Chen Yan Jialin Jiang Fanqi Kong Jiangang Shi |
| author_facet | Jian Zhu Ruping Sun Kaiqiang Sun Chen Yan Jialin Jiang Fanqi Kong Jiangang Shi |
| author_sort | Jian Zhu |
| collection | DOAJ |
| description | Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3−/−) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11−/−) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD. |
| first_indexed | 2024-04-09T13:30:05Z |
| format | Article |
| id | doaj.art-e0fa1ff6de4f48309f6b84512cfa82c6 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-09T13:30:05Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-e0fa1ff6de4f48309f6b84512cfa82c62023-05-10T04:19:12ZengElsevierRedox Biology2213-23172023-06-0162102707The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3Jian Zhu0Ruping Sun1Kaiqiang Sun2Chen Yan3Jialin Jiang4Fanqi Kong5Jiangang Shi6Department of Orthopedics, Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, ChinaSchool of Health Science and Engineering, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai, 200093, ChinaDepartment of Orthopaedic Surgery, Naval Medical Center, Naval Medical University, Shanghai, 200433, ChinaDepartment of Orthopedics, Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, ChinaDepartment of Orthopedics, Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, ChinaDepartment of Orthopedics, Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, ChinaDepartment of Orthopedics, Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, China; Corresponding author. Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University No.415 Fengyang Road, Shanghai, 200003, People's Republic of China.Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3−/−) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11−/−) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD.http://www.sciencedirect.com/science/article/pii/S2213231723001088USP11Sirt3Oxidative stress-induced ferroptosisIVDDDe-ubiquitination |
| spellingShingle | Jian Zhu Ruping Sun Kaiqiang Sun Chen Yan Jialin Jiang Fanqi Kong Jiangang Shi The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 Redox Biology USP11 Sirt3 Oxidative stress-induced ferroptosis IVDD De-ubiquitination |
| title | The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 |
| title_full | The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 |
| title_fullStr | The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 |
| title_full_unstemmed | The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 |
| title_short | The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3 |
| title_sort | deubiquitinase usp11 ameliorates intervertebral disc degeneration by regulating oxidative stress induced ferroptosis via deubiquitinating and stabilizing sirt3 |
| topic | USP11 Sirt3 Oxidative stress-induced ferroptosis IVDD De-ubiquitination |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723001088 |
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