Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes

Yunjung Jin; Youn Wook Chung; Min Kyo Jung; Jea Hwang Lee; Kwan Young Ko; Jun Ki Jang; Minju Ham; Hyunwoo Kang; Chan Gi Pack; Hisaaki Mihara; Ick Young Kim

doi:10.1007/s00018-019-03287-y

Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes

Yunjung Jin, Youn Wook Chung, Min Kyo Jung, Jea Hwang Lee, Kwan Young Ko, Jun Ki Jang, Minju Ham, Hyunwoo Kang, Chan Gi Pack, Hisaaki Mihara, Ick Young Kim

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood–brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE) through heparin-binding sites of SELENOP, and the interaction regulated the secretion of exosomal SELENOP. Using in vitro BBB model of transwell cell culture, exosomal SELENOP was found to supply Se to brain endothelial cells and neuronal cells, which synthesized selenoproteins by a process regulated by ApoE and ApoER2. The regulatory role of ApoE in SELENOP transport was also observed in vivo using ApoE^−/− mice. Exosomal SELENOP transport protected neuronal cells from amyloid β (Aβ)-induced cell death. Taken together, our results suggest a new delivery mechanism for Se to neuronal cells by exosomal SELENOP.

Original language	English
Pages (from-to)	2367-2386
Number of pages	20
Journal	Cellular and Molecular Life Sciences
Volume	77
Issue number	12
DOIs	https://doi.org/10.1007/s00018-019-03287-y
Publication status	Published - 2020 Jun 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services.

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services.

Publisher Copyright:
© 2019, Springer Nature Switzerland AG.

Keywords

Amyloid β
Apolipoprotein E
Exosome
Protein transport
Selenoprotein P

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Pharmacology
Cellular and Molecular Neuroscience
Cell Biology

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10.1007/s00018-019-03287-y

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title = "Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes",

abstract = "Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood–brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE) through heparin-binding sites of SELENOP, and the interaction regulated the secretion of exosomal SELENOP. Using in vitro BBB model of transwell cell culture, exosomal SELENOP was found to supply Se to brain endothelial cells and neuronal cells, which synthesized selenoproteins by a process regulated by ApoE and ApoER2. The regulatory role of ApoE in SELENOP transport was also observed in vivo using ApoE−/− mice. Exosomal SELENOP transport protected neuronal cells from amyloid β (Aβ)-induced cell death. Taken together, our results suggest a new delivery mechanism for Se to neuronal cells by exosomal SELENOP.",

keywords = "Amyloid β, Apolipoprotein E, Exosome, Protein transport, Selenoprotein P",

author = "Yunjung Jin and Chung, {Youn Wook} and Jung, {Min Kyo} and Lee, {Jea Hwang} and Ko, {Kwan Young} and Jang, {Jun Ki} and Minju Ham and Hyunwoo Kang and Pack, {Chan Gi} and Hisaaki Mihara and Kim, {Ick Young}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services. Publisher Copyright: {\textcopyright} 2019, Springer Nature Switzerland AG.",

year = "2020",

month = jun,

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doi = "10.1007/s00018-019-03287-y",

language = "English",

volume = "77",

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T1 - Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes

AU - Jin, Yunjung

AU - Chung, Youn Wook

AU - Jung, Min Kyo

AU - Lee, Jea Hwang

AU - Ko, Kwan Young

AU - Jang, Jun Ki

AU - Ham, Minju

AU - Kang, Hyunwoo

AU - Pack, Chan Gi

AU - Mihara, Hisaaki

AU - Kim, Ick Young

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1A2B4009525). This work was also supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015H1A2A1033613). This work was also partially supported by a Korea University Grant. We also thank the Electron Microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation for providing the valuable technical services. Publisher Copyright: © 2019, Springer Nature Switzerland AG.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood–brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE) through heparin-binding sites of SELENOP, and the interaction regulated the secretion of exosomal SELENOP. Using in vitro BBB model of transwell cell culture, exosomal SELENOP was found to supply Se to brain endothelial cells and neuronal cells, which synthesized selenoproteins by a process regulated by ApoE and ApoER2. The regulatory role of ApoE in SELENOP transport was also observed in vivo using ApoE−/− mice. Exosomal SELENOP transport protected neuronal cells from amyloid β (Aβ)-induced cell death. Taken together, our results suggest a new delivery mechanism for Se to neuronal cells by exosomal SELENOP.

AB - Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood–brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE) through heparin-binding sites of SELENOP, and the interaction regulated the secretion of exosomal SELENOP. Using in vitro BBB model of transwell cell culture, exosomal SELENOP was found to supply Se to brain endothelial cells and neuronal cells, which synthesized selenoproteins by a process regulated by ApoE and ApoER2. The regulatory role of ApoE in SELENOP transport was also observed in vivo using ApoE−/− mice. Exosomal SELENOP transport protected neuronal cells from amyloid β (Aβ)-induced cell death. Taken together, our results suggest a new delivery mechanism for Se to neuronal cells by exosomal SELENOP.

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Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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