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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,...

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Autores principales: Gu, Hai-Ping, Wu, Xiao-Feng, Gong, Ya-Ting, Mu-Yao Wu, Shi, Meng-Ying, Sun, Ya-ming, Dang, Bao-Qi, Chen, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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