Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice
Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age...
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doaj-0f995bef6a5846038ceb887ea925f60e2021-01-24T04:27:41ZengElsevierRedox Biology2213-23172021-04-0140101865Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in miceJuan Ma0Christopher Qian1Yong Bao2Meng-Yue Liu3Hui-Min Ma4Meng-Qi Shen5Wei Li6Jiao-Jiao Wang7Yu-Xin Bao8Yong Liu9Ya Ke10Zhong-Ming Qian11Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China; Laboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, 201203, ChinaSchool of Biomedical Sciences and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, ChinaInstitute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, ChinaInstitute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, ChinaInstitute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, ChinaInstitute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, ChinaInstitute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, ChinaLaboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, 201203, China; Research Center for Medicine and Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, ChinaResearch Center for Medicine and Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, ChinaDepartment of Pain and Rehabilitation, The Second Affiliated Hospital, The Army Medical University, Chongqing, ChinaSchool of Biomedical Sciences and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China; Corresponding author.Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China; Laboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, 201203, China; Corresponding author. Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China.Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1. Furthermore, replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. The findings imply that ApoE may be essential for body iron homeostasis and also suggest that clinical late-onset diseases with unexplained iron abnormality may partly be related to deficiency or reduced expression of ApoE.http://www.sciencedirect.com/science/article/pii/S2213231721000136Apolipoprotein E knock-out (ApoE−/-) miceIron in liver and spleenTransferrin receptor 1 (TfR1)Ferroportin 1 (Fpn1)HepcidinNuclear factor erythroid 2-related factor-2 (Nrf2) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan Ma Christopher Qian Yong Bao Meng-Yue Liu Hui-Min Ma Meng-Qi Shen Wei Li Jiao-Jiao Wang Yu-Xin Bao Yong Liu Ya Ke Zhong-Ming Qian |
spellingShingle |
Juan Ma Christopher Qian Yong Bao Meng-Yue Liu Hui-Min Ma Meng-Qi Shen Wei Li Jiao-Jiao Wang Yu-Xin Bao Yong Liu Ya Ke Zhong-Ming Qian Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice Redox Biology Apolipoprotein E knock-out (ApoE−/-) mice Iron in liver and spleen Transferrin receptor 1 (TfR1) Ferroportin 1 (Fpn1) Hepcidin Nuclear factor erythroid 2-related factor-2 (Nrf2) |
author_facet |
Juan Ma Christopher Qian Yong Bao Meng-Yue Liu Hui-Min Ma Meng-Qi Shen Wei Li Jiao-Jiao Wang Yu-Xin Bao Yong Liu Ya Ke Zhong-Ming Qian |
author_sort |
Juan Ma |
title |
Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice |
title_short |
Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice |
title_full |
Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice |
title_fullStr |
Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice |
title_full_unstemmed |
Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice |
title_sort |
apolipoprotein e deficiency induces a progressive increase in tissue iron contents with age in mice |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2021-04-01 |
description |
Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1. Furthermore, replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. The findings imply that ApoE may be essential for body iron homeostasis and also suggest that clinical late-onset diseases with unexplained iron abnormality may partly be related to deficiency or reduced expression of ApoE. |
topic |
Apolipoprotein E knock-out (ApoE−/-) mice Iron in liver and spleen Transferrin receptor 1 (TfR1) Ferroportin 1 (Fpn1) Hepcidin Nuclear factor erythroid 2-related factor-2 (Nrf2) |
url |
http://www.sciencedirect.com/science/article/pii/S2213231721000136 |
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