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RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats
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,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395478/ https://www.ncbi.nlm.nih.gov/pubmed/37539293 http://dx.doi.org/10.1016/j.heliyon.2023.e18160 |
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author | Gu, Hai-Ping Wu, Xiao-Feng Gong, Ya-Ting Mu-Yao Wu Shi, Meng-Ying Sun, Ya-ming Dang, Bao-Qi Chen, Gang |
author_facet | Gu, Hai-Ping Wu, Xiao-Feng Gong, Ya-Ting Mu-Yao Wu Shi, Meng-Ying Sun, Ya-ming Dang, Bao-Qi Chen, Gang |
author_sort | Gu, Hai-Ping |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10395478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103954782023-08-03 RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats Gu, Hai-Ping Wu, Xiao-Feng Gong, Ya-Ting Mu-Yao Wu Shi, Meng-Ying Sun, Ya-ming Dang, Bao-Qi Chen, Gang Heliyon Research Article 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. Elsevier 2023-07-12 /pmc/articles/PMC10395478/ /pubmed/37539293 http://dx.doi.org/10.1016/j.heliyon.2023.e18160 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Gu, Hai-Ping Wu, Xiao-Feng Gong, Ya-Ting Mu-Yao Wu Shi, Meng-Ying Sun, Ya-ming Dang, Bao-Qi Chen, Gang RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats |
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 | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395478/ https://www.ncbi.nlm.nih.gov/pubmed/37539293 http://dx.doi.org/10.1016/j.heliyon.2023.e18160 |
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