Cargando…
14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos
To investigate the effect of 14,15-EET on the parthanatos in neurons induced by cerebral ischemia and reperfusion, middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral ischemia reperfusion in vivo and in vitro,...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471287/ https://www.ncbi.nlm.nih.gov/pubmed/34575823 http://dx.doi.org/10.3390/ijms22189660 |
_version_ | 1784574425744539648 |
---|---|
author | Zhao, Haipeng Tang, Jing Chen, Hongyang Gu, Wei Geng, Huixia Wang, Lai Wang, Yanming |
author_facet | Zhao, Haipeng Tang, Jing Chen, Hongyang Gu, Wei Geng, Huixia Wang, Lai Wang, Yanming |
author_sort | Zhao, Haipeng |
collection | PubMed |
description | To investigate the effect of 14,15-EET on the parthanatos in neurons induced by cerebral ischemia and reperfusion, middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral ischemia reperfusion in vivo and in vitro, respectively. TTC staining and the Tunel method were used to detect cerebral infarct volume and neuronal apoptosis. Western blot and immunofluorescence were used to detect poly (ADP-ribose) polymerase-1 (PARP-1) activation and AIF nuclear translocation. The production of reactive oxygen species (ROS) and the expression of antioxidant genes were detected by Mito SOX, DCFH-DA and qPCR methods. MCAO/R increased cerebral infarct volume and neuronal apoptosis in mice, while 14,15-EET pretreatment increased cerebral infarct volume and neuronal apoptosis. OGD/R induced reactive oxygen species generation, PARP-1 cleavage, and AIF nuclear translocation in cortical neurons. 14,15-EET pretreatment could enhance the antioxidant gene expression of glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in cortical neurons after ischemia and reperfusion. 14,15-EET inhibits the neuronal parthanatos induced by MCAO/R through upregulation of the expression of antioxidant genes and by reducing the generation of reactive oxygen species. This study advances the EET neuroprotection theory and provides a scientific basis for targeted clinical drugs that reduce neuronal parthanatos following cerebral ischemia and reperfusion. |
format | Online Article Text |
id | pubmed-8471287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84712872021-09-27 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos Zhao, Haipeng Tang, Jing Chen, Hongyang Gu, Wei Geng, Huixia Wang, Lai Wang, Yanming Int J Mol Sci Article To investigate the effect of 14,15-EET on the parthanatos in neurons induced by cerebral ischemia and reperfusion, middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral ischemia reperfusion in vivo and in vitro, respectively. TTC staining and the Tunel method were used to detect cerebral infarct volume and neuronal apoptosis. Western blot and immunofluorescence were used to detect poly (ADP-ribose) polymerase-1 (PARP-1) activation and AIF nuclear translocation. The production of reactive oxygen species (ROS) and the expression of antioxidant genes were detected by Mito SOX, DCFH-DA and qPCR methods. MCAO/R increased cerebral infarct volume and neuronal apoptosis in mice, while 14,15-EET pretreatment increased cerebral infarct volume and neuronal apoptosis. OGD/R induced reactive oxygen species generation, PARP-1 cleavage, and AIF nuclear translocation in cortical neurons. 14,15-EET pretreatment could enhance the antioxidant gene expression of glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in cortical neurons after ischemia and reperfusion. 14,15-EET inhibits the neuronal parthanatos induced by MCAO/R through upregulation of the expression of antioxidant genes and by reducing the generation of reactive oxygen species. This study advances the EET neuroprotection theory and provides a scientific basis for targeted clinical drugs that reduce neuronal parthanatos following cerebral ischemia and reperfusion. MDPI 2021-09-07 /pmc/articles/PMC8471287/ /pubmed/34575823 http://dx.doi.org/10.3390/ijms22189660 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhao, Haipeng Tang, Jing Chen, Hongyang Gu, Wei Geng, Huixia Wang, Lai Wang, Yanming 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title | 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title_full | 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title_fullStr | 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title_full_unstemmed | 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title_short | 14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos |
title_sort | 14,15-eet reduced brain injury from cerebral ischemia and reperfusion via suppressing neuronal parthanatos |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471287/ https://www.ncbi.nlm.nih.gov/pubmed/34575823 http://dx.doi.org/10.3390/ijms22189660 |
work_keys_str_mv | AT zhaohaipeng 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT tangjing 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT chenhongyang 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT guwei 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT genghuixia 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT wanglai 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos AT wangyanming 1415eetreducedbraininjuryfromcerebralischemiaandreperfusionviasuppressingneuronalparthanatos |