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

Research output: Contribution to journalArticle

1 Citation (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 languageEnglish
JournalCellular and Molecular Life Sciences
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Selenoprotein P
Exosomes
Apolipoproteins E
Selenium
Hepatocytes
Plasma Kallikrein
Selenoproteins
Brain
Amyloid

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

Cite this

Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes. / Jin, Yunjung; Chung, Youn Wook; Jung, Min Kyo; Lee, Jea Hwang; Ko, Kwan Young; Jang, Jun Ki; Ham, Minju; Kang, Hyunwoo; Pack, Chan Gi; Mihara, Hisaaki; Kim, Ick Young.

In: Cellular and Molecular Life Sciences, 01.01.2019.

Research output: Contribution to journalArticle

Jin, Yunjung ; Chung, Youn Wook ; Jung, Min Kyo ; Lee, Jea Hwang ; Ko, Kwan Young ; Jang, Jun Ki ; Ham, Minju ; Kang, Hyunwoo ; Pack, Chan Gi ; Mihara, Hisaaki ; Kim, Ick Young. / Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes. In: Cellular and Molecular Life Sciences. 2019.
@article{bf4eb99aa6674d979f73b5c9832a4816,
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}",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00018-019-03287-y",
language = "English",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",

}

TY - JOUR

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

PY - 2019/1/1

Y1 - 2019/1/1

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.

KW - Amyloid β

KW - Apolipoprotein E

KW - Exosome

KW - Protein transport

KW - Selenoprotein P

UR - http://www.scopus.com/inward/record.url?scp=85071435607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071435607&partnerID=8YFLogxK

U2 - 10.1007/s00018-019-03287-y

DO - 10.1007/s00018-019-03287-y

M3 - Article

AN - SCOPUS:85071435607

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

ER -