Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice
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
Affiliations
Juan Ma
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
Christopher Qian
School of Biomedical Sciences and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
Yong Bao
Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China
Meng-Yue Liu
Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China
Hui-Min Ma
Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China
Meng-Qi Shen
Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China
Wei Li
Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, 226001, China
Jiao-Jiao Wang
Laboratory 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, China
Yu-Xin Bao
Research Center for Medicine and Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, China
Yong Liu
Department of Pain and Rehabilitation, The Second Affiliated Hospital, The Army Medical University, Chongqing, China
Ya Ke
School of Biomedical Sciences and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China; Corresponding author.
Zhong-Ming Qian
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.
