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miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models

We investigated the role of microRNA (miR)-485 and its downstream signaling molecules on mediating epilepsy in cellular and rat models. We established a cellular epilepsy model by exposing hippocampal neurons to magnesium and a rat model by treating ICR mice with lithium chloride (127 mg/kg) and pil...

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Autores principales: Pan, Wei, Song, Xingyu, Hu, Qibo, Zhang, Yunfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202868/
https://www.ncbi.nlm.nih.gov/pubmed/34021541
http://dx.doi.org/10.18632/aging.203058
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author Pan, Wei
Song, Xingyu
Hu, Qibo
Zhang, Yunfeng
author_facet Pan, Wei
Song, Xingyu
Hu, Qibo
Zhang, Yunfeng
author_sort Pan, Wei
collection PubMed
description We investigated the role of microRNA (miR)-485 and its downstream signaling molecules on mediating epilepsy in cellular and rat models. We established a cellular epilepsy model by exposing hippocampal neurons to magnesium and a rat model by treating ICR mice with lithium chloride (127 mg/kg) and pilocarpine (30 mg/kg). We confirmed that miR-485 could bind and inhibit histone deacetylase 5 (HDAC5) and then measured expression of miR-485 and in mice and cells. Cells were transfected with overexpression or knockdown of miR-485, HDAC5, hypoxia-inducible factor-1alpha (HIF1α), or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme (PFKFB3) to verify their roles in apoptosis, oxidative stress, and inflammation in epileptic hippocampal neurons. Binding relationship between miR-485, HDAC5, HIF1α, and PFKFB3 was verified. Oxidative stress and inflammation marker levels in epilepsy model mice were assessed. miR-485 was downregulated and HDAC5 was upregulated in cell and animal model of epilepsy. Seizure, neuronal apoptosis, oxidative stress (increased SOD and GSH-Px expression and decreased MDA and 8-OHdG expression) and inflammation (reduced IL-1β, TNF-α, and IL-6 expression) were reduced by miR-485 in epileptic cells. HIF1α and PFKFB3 expression was reduced by HDAC5 knockdown in cells, which was recapitulated in vivo. Thus, miR-485 alleviates neuronal damage and epilepsy by inhibiting HDAC5, HIF1α, and PFKFB3.
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spelling pubmed-82028682021-06-15 miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models Pan, Wei Song, Xingyu Hu, Qibo Zhang, Yunfeng Aging (Albany NY) Research Paper We investigated the role of microRNA (miR)-485 and its downstream signaling molecules on mediating epilepsy in cellular and rat models. We established a cellular epilepsy model by exposing hippocampal neurons to magnesium and a rat model by treating ICR mice with lithium chloride (127 mg/kg) and pilocarpine (30 mg/kg). We confirmed that miR-485 could bind and inhibit histone deacetylase 5 (HDAC5) and then measured expression of miR-485 and in mice and cells. Cells were transfected with overexpression or knockdown of miR-485, HDAC5, hypoxia-inducible factor-1alpha (HIF1α), or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme (PFKFB3) to verify their roles in apoptosis, oxidative stress, and inflammation in epileptic hippocampal neurons. Binding relationship between miR-485, HDAC5, HIF1α, and PFKFB3 was verified. Oxidative stress and inflammation marker levels in epilepsy model mice were assessed. miR-485 was downregulated and HDAC5 was upregulated in cell and animal model of epilepsy. Seizure, neuronal apoptosis, oxidative stress (increased SOD and GSH-Px expression and decreased MDA and 8-OHdG expression) and inflammation (reduced IL-1β, TNF-α, and IL-6 expression) were reduced by miR-485 in epileptic cells. HIF1α and PFKFB3 expression was reduced by HDAC5 knockdown in cells, which was recapitulated in vivo. Thus, miR-485 alleviates neuronal damage and epilepsy by inhibiting HDAC5, HIF1α, and PFKFB3. Impact Journals 2021-05-21 /pmc/articles/PMC8202868/ /pubmed/34021541 http://dx.doi.org/10.18632/aging.203058 Text en Copyright: © 2021 Pan et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pan, Wei
Song, Xingyu
Hu, Qibo
Zhang, Yunfeng
miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title_full miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title_fullStr miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title_full_unstemmed miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title_short miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models
title_sort mir-485 inhibits histone deacetylase hdac5, hif1α and pfkfb3 expression to alleviate epilepsy in cellular and rodent models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202868/
https://www.ncbi.nlm.nih.gov/pubmed/34021541
http://dx.doi.org/10.18632/aging.203058
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