RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats
Background: Histone deacetylase 3 (HDAC3) restores chromatin nucleosomes to a transcriptional repression state, thereby inhibiting gene expression. Studies have found that HDAC3 expression is upregulated in a variety of pathological states of the central nervous system and related to its neurotoxici...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023053689 |
| _version_ | 1797771466195861504 |
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| author | Hai-Ping Gu Xiao-Feng Wu Ya-Ting Gong Mu-Yao Wu Meng-Ying Shi Ya-ming Sun Bao-Qi Dang Gang Chen |
| author_facet | Hai-Ping Gu Xiao-Feng Wu Ya-Ting Gong Mu-Yao Wu Meng-Ying Shi Ya-ming Sun Bao-Qi Dang Gang Chen |
| author_sort | Hai-Ping Gu |
| collection | DOAJ |
| description | Background: Histone deacetylase 3 (HDAC3) restores chromatin nucleosomes to a transcriptional repression state, thereby inhibiting gene expression. Studies have found that HDAC3 expression is upregulated in a variety of pathological states of the central nervous system and related to its neurotoxicity. However, the role of HDAC3 in surgical brain injury (SBI) has not been thoroughly explored. Objective: To observe the role of HDAC3 in SBI and the outcome of SBI after its suppression. Methods: Rat SBI model was used, and intraperitoneal injection of RGFP966 (HDAC3 specific inhibitor) was used to detect the changes of HDAC3 expression and neuronal apoptosis indexes in the surrounding cortex of SBI rats, and the cerebral edema and neurological outcome of rats were observed. Results: The expression of HDAC3 in the peripheral cortex of SBI rats was increased, and RGFP966 inhibited the upregulation of HDAC3 and saved the nerve cells around the damaged area. In addition, RGFP966 increased the expression of anti-oxidative stress proteins such as heme oxygenase-1 (HO-1) and superoxide dismutase 2 (SOD2). At the same time, the expression of apoptotic marker protein cleaved-caspase-3 (cle-caspase-3) was decreased, while the expression level of apoptotic protective marker protein B-cell lymphoma 2 (Bcl-2) was increased. In addition, this research demonstrated that in the RGFP966 rat SBI model, the expression level of antioxidant modifier nuclear factor-erythroid 2-related factor 2 (Nrf2) was increased. Conclusion: RGFP966 might activate HDAC3/Nrf2 signaling pathway by inhibiting HDAC3, regulated oxidative stress and nerve cell apoptosis induced by SBI in rat SBI model, reduced brain edema, and had a protective effect on nerve injury. It might be a potential target of SBI pathology. |
| first_indexed | 2024-03-12T21:37:58Z |
| format | Article |
| id | doaj.art-ef5c61bb9bd648b386cdb649f175b00c |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T21:37:58Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-ef5c61bb9bd648b386cdb649f175b00c2023-07-27T05:58:44ZengElsevierHeliyon2405-84402023-07-0197e18160RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in ratsHai-Ping Gu0Xiao-Feng Wu1Ya-Ting Gong2 Mu-Yao Wu3Meng-Ying Shi4Ya-ming Sun5Bao-Qi Dang6Gang Chen7Department of Neurology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Anesthesiology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Neurology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China; Corresponding author. Department of Neurology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, No.77 Changan Southern Road, Suzhou 215600, ChinaDepartment of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China; Corresponding author. Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, No.77 Changan Southern Road, Suzhou 215600, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, ChinaBackground: Histone deacetylase 3 (HDAC3) restores chromatin nucleosomes to a transcriptional repression state, thereby inhibiting gene expression. Studies have found that HDAC3 expression is upregulated in a variety of pathological states of the central nervous system and related to its neurotoxicity. However, the role of HDAC3 in surgical brain injury (SBI) has not been thoroughly explored. Objective: To observe the role of HDAC3 in SBI and the outcome of SBI after its suppression. Methods: Rat SBI model was used, and intraperitoneal injection of RGFP966 (HDAC3 specific inhibitor) was used to detect the changes of HDAC3 expression and neuronal apoptosis indexes in the surrounding cortex of SBI rats, and the cerebral edema and neurological outcome of rats were observed. Results: The expression of HDAC3 in the peripheral cortex of SBI rats was increased, and RGFP966 inhibited the upregulation of HDAC3 and saved the nerve cells around the damaged area. In addition, RGFP966 increased the expression of anti-oxidative stress proteins such as heme oxygenase-1 (HO-1) and superoxide dismutase 2 (SOD2). At the same time, the expression of apoptotic marker protein cleaved-caspase-3 (cle-caspase-3) was decreased, while the expression level of apoptotic protective marker protein B-cell lymphoma 2 (Bcl-2) was increased. In addition, this research demonstrated that in the RGFP966 rat SBI model, the expression level of antioxidant modifier nuclear factor-erythroid 2-related factor 2 (Nrf2) was increased. Conclusion: RGFP966 might activate HDAC3/Nrf2 signaling pathway by inhibiting HDAC3, regulated oxidative stress and nerve cell apoptosis induced by SBI in rat SBI model, reduced brain edema, and had a protective effect on nerve injury. It might be a potential target of SBI pathology.http://www.sciencedirect.com/science/article/pii/S2405844023053689Surgical brain injuryRGFP966HDAC3HDAC3/Nrf2 signal pathwayOxidative stress |
| spellingShingle | Hai-Ping Gu Xiao-Feng Wu Ya-Ting Gong Mu-Yao Wu Meng-Ying Shi Ya-ming Sun Bao-Qi Dang Gang Chen RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats Heliyon Surgical brain injury RGFP966 HDAC3 HDAC3/Nrf2 signal pathway Oxidative stress |
| title | RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
| title_full | RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
| title_fullStr | RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
| title_full_unstemmed | RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
| title_short | RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
| title_sort | rgfp966 exerts neuroprotective effect via hdac3 nrf2 pathway after surgical brain injury in rats |
| topic | Surgical brain injury RGFP966 HDAC3 HDAC3/Nrf2 signal pathway Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023053689 |
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