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Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats

Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR....

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Autor principal: Guo, Yongqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716744/
https://www.ncbi.nlm.nih.gov/pubmed/29228704
http://dx.doi.org/10.18632/oncotarget.21445
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author Guo, Yongqing
author_facet Guo, Yongqing
author_sort Guo, Yongqing
collection PubMed
description Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival. in vitro, HIF-1a induced up-regulation of BNIP3 and NIX in human cortical neuron cells, HCN-1A. Inhibition of BNIP3 and NIX significantly attenuated HIF-1a-suppressed cell apoptosis and HIF-1a-induced cell autophagy. Together, these data suggest that HIF-1a may ameliorate brain damages during IR through BNIP3 and NIX -dependent augmentation of autophagic cell survival and reduction in cell apoptosis.
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spelling pubmed-57167442017-12-08 Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats Guo, Yongqing Oncotarget Research Paper Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival. in vitro, HIF-1a induced up-regulation of BNIP3 and NIX in human cortical neuron cells, HCN-1A. Inhibition of BNIP3 and NIX significantly attenuated HIF-1a-suppressed cell apoptosis and HIF-1a-induced cell autophagy. Together, these data suggest that HIF-1a may ameliorate brain damages during IR through BNIP3 and NIX -dependent augmentation of autophagic cell survival and reduction in cell apoptosis. Impact Journals LLC 2017-10-01 /pmc/articles/PMC5716744/ /pubmed/29228704 http://dx.doi.org/10.18632/oncotarget.21445 Text en Copyright: © 2017 Guo http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Guo, Yongqing
Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title_full Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title_fullStr Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title_full_unstemmed Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title_short Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
title_sort role of hif-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716744/
https://www.ncbi.nlm.nih.gov/pubmed/29228704
http://dx.doi.org/10.18632/oncotarget.21445
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