Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes

Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explore...

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Main Authors: Qiong Zhou, Yangfang An, Yonghong Tang
Format: Article
Language:English
Published: IMR Press 2019-12-01
Series:Journal of Integrative Neuroscience
Subjects:
Online Access: https://jin.imrpress.com/fileup/1757-448X/PDF/1577791323374-569558607.pdf
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author Qiong Zhou
Yangfang An
Yonghong Tang
author_facet Qiong Zhou
Yangfang An
Yonghong Tang
author_sort Qiong Zhou
collection DOAJ
description Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explored the expression pattern and function of the regulator of reprogramming in cerebral hypoxia-induced injury. The expression pattern and the function of the regulator of reprogramming were explored in mice with middle cerebral artery occlusion, and human brain microvascular endothelial cells underwent oxygen-glucose deprivation treatment. A case-control study, including 223 ischemic stroke patients and 155 controls were also conducted to investigate its correlation with ischemic stroke clinical characteristics. Results showed that the regulator of reprogramming increased significantly in middle cerebral artery occlusion in mice (P < 0.05), and its level remained stable within 2 to 48 h after the implement of middle cerebral artery occlusion. Oxygen-glucose deprivation up-regulated the expression of regulator of reprogramming, and regulator of reprogramming promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, while small interfering ribonucleic acid (RNA) targeting regulator of reprogramming amplified these effects. Regulator of reprogramming increased and maintained stable within 3 to 48 h of ischemic stroke onset in patients, and was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) (r = -0.708, P < 0.001), high sensitivity C-reactive protein (Hs-CRP) (r = -0.683, P < 0.001) level, infarct volume (r = -0.579, P < 0.001), and modified Rankin scale (mRS) (r = -0.728, P < 0.001). These results indicate that the regulator of reprogramming can alleviate cerebral hypoxia-induced injury by suppressing TNFα-induced apoptosis of vascular endothelial cells.
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spelling doaj.art-f6c3a6e8da53402d98fac9f0f9b1b9342022-12-22T00:26:51ZengIMR PressJournal of Integrative Neuroscience0219-63521757-448X2019-12-0118443143710.31083/j.jin.2019.04.11941577791323374-569558607Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexesQiong Zhou0Yangfang An1Yonghong Tang2 Department of Neurology, Yiyang Central Hospital, No. 336 Dongfengnan Road, Hengyang City, Hunan Province, 413000, P. R. China Department of Neurology, Yiyang Central Hospital, No. 336 Dongfengnan Road, Hengyang City, Hunan Province, 413000, P. R. China Department of Neurology, Yiyang Central Hospital, No. 336 Dongfengnan Road, Hengyang City, Hunan Province, 413000, P. R. China Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explored the expression pattern and function of the regulator of reprogramming in cerebral hypoxia-induced injury. The expression pattern and the function of the regulator of reprogramming were explored in mice with middle cerebral artery occlusion, and human brain microvascular endothelial cells underwent oxygen-glucose deprivation treatment. A case-control study, including 223 ischemic stroke patients and 155 controls were also conducted to investigate its correlation with ischemic stroke clinical characteristics. Results showed that the regulator of reprogramming increased significantly in middle cerebral artery occlusion in mice (P < 0.05), and its level remained stable within 2 to 48 h after the implement of middle cerebral artery occlusion. Oxygen-glucose deprivation up-regulated the expression of regulator of reprogramming, and regulator of reprogramming promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, while small interfering ribonucleic acid (RNA) targeting regulator of reprogramming amplified these effects. Regulator of reprogramming increased and maintained stable within 3 to 48 h of ischemic stroke onset in patients, and was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) (r = -0.708, P < 0.001), high sensitivity C-reactive protein (Hs-CRP) (r = -0.683, P < 0.001) level, infarct volume (r = -0.579, P < 0.001), and modified Rankin scale (mRS) (r = -0.728, P < 0.001). These results indicate that the regulator of reprogramming can alleviate cerebral hypoxia-induced injury by suppressing TNFα-induced apoptosis of vascular endothelial cells. https://jin.imrpress.com/fileup/1757-448X/PDF/1577791323374-569558607.pdf ischemic strokehypoxialong non-coding rnathe regulator of reprogrammingapoptosis complexesmice model
spellingShingle Qiong Zhou
Yangfang An
Yonghong Tang
Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
Journal of Integrative Neuroscience
ischemic stroke
hypoxia
long non-coding rna
the regulator of reprogramming
apoptosis complexes
mice model
title Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
title_full Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
title_fullStr Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
title_full_unstemmed Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
title_short Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes
title_sort long noncoding rna regulator of reprogramming alleviates hypoxia induced cerebral injury in mice model and human via modulating apoptosis complexes
topic ischemic stroke
hypoxia
long non-coding rna
the regulator of reprogramming
apoptosis complexes
mice model
url https://jin.imrpress.com/fileup/1757-448X/PDF/1577791323374-569558607.pdf
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AT yangfangan longnoncodingrnaregulatorofreprogrammingalleviateshypoxiainducedcerebralinjuryinmicemodelandhumanviamodulatingapoptosiscomplexes
AT yonghongtang longnoncodingrnaregulatorofreprogrammingalleviateshypoxiainducedcerebralinjuryinmicemodelandhumanviamodulatingapoptosiscomplexes