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

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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

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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

Jin, Y., Chung, Y. W., Jung, M. K., Lee, J. H., Ko, K. Y., Jang, J. K., Ham, M., Kang, H., Pack, C. G., Mihara, H., & Kim, I. Y. (Accepted/In press). Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-019-03287-y