Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons

Abstract Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the...

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Autores principales:	Hongxia Li, Caixia Zhang, Hui Shen, Zhilei Shen, Lusha Wu, Fengfeng Mo, Min Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc84a5bfbcb44af9b21a443d066c2eca
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spelling	oai:doaj.org-article:cc84a5bfbcb44af9b21a443d066c2eca2021-12-02T12:32:01ZPhysiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons10.1038/s41598-017-06058-62045-2322https://doaj.org/article/cc84a5bfbcb44af9b21a443d066c2eca2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06058-6https://doaj.org/toc/2045-2322Abstract Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains. We demonstrated that Glucocorticoid (GC), which is largely secreted under stress, could up-regulate HCP1 expression, thus promoting heme uptake in neurons. We also ascertained that HCP1 expression can be induced by GC through a transcription factor, Krüppel-like factor 4 (KLF4). These results may gain new insights into the etiology of heme uptake and iron accumulation in PS rats, and find new therapeutic targets of iron accumulation in Parkinson’s disease or Alzheimer’s disease.Hongxia LiCaixia ZhangHui ShenZhilei ShenLusha WuFengfeng MoMin LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hongxia Li Caixia Zhang Hui Shen Zhilei Shen Lusha Wu Fengfeng Mo Min Li Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
description	Abstract Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains. We demonstrated that Glucocorticoid (GC), which is largely secreted under stress, could up-regulate HCP1 expression, thus promoting heme uptake in neurons. We also ascertained that HCP1 expression can be induced by GC through a transcription factor, Krüppel-like factor 4 (KLF4). These results may gain new insights into the etiology of heme uptake and iron accumulation in PS rats, and find new therapeutic targets of iron accumulation in Parkinson’s disease or Alzheimer’s disease.
format	article
author	Hongxia Li Caixia Zhang Hui Shen Zhilei Shen Lusha Wu Fengfeng Mo Min Li
author_facet	Hongxia Li Caixia Zhang Hui Shen Zhilei Shen Lusha Wu Fengfeng Mo Min Li
author_sort	Hongxia Li
title	Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
title_short	Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
title_full	Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
title_fullStr	Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
title_full_unstemmed	Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons
title_sort	physiological stress-induced corticosterone increases heme uptake via klf4-hcp1 signaling pathway in hippocampus neurons
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cc84a5bfbcb44af9b21a443d066c2eca
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Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons

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