Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes
Open accessAbstract
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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ApoE is known to import selenoprotein P (SELENOP), a major selenium-containing protein in plasma required for the synthesis of selenoenzymes such as GPX4.
“ApoE is known to import selenoprotein P (SELENOP), a major selenium (Se)–containing protein in plasma that is required for the synthesis of selenoenzymes such as GPX4 (38, 39).”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [38]
The Introduction says SELENOP accounts for 50% of plasma selenium and supplies selenium for production of other selenoproteins. But the Results and Discussion describe ApoE as negatively regulating exosomal SELENOP uptake, not as an established importer; the Discussion presents a possible role in guiding uptake as a hypothesis requiring further study. The copy does not identify GPX4 as an example. (LLM, conf=0.86)
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Cites
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Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis
More, S., Bonnereau, J., Wouters, D., Spotbeen, X., Karras, P., Rizzollo, F., Killian, T., Venken, T., Naulaerts, S., Vervoort, E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adp6164 · Cited by 25 · see citing works
- Authors
- 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.
- Affiliations
- Korea University (KR)
- Yonsei University (KR)
- Asan Medical Center (KR)
- Harvard University (US)
- Ritsumeikan University (JP)
- Corresponding author
- Kim, Ick Young
- ORCID
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2019-08-30
- Volume
- 77
- Issue
- 12
- Pages
- 2367-2386
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11104972
- OpenAlex
- W2970911355
- Cited by
- 39
- References
- 3
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 12 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 1 · 2019: 1
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Research Foundation of Korea (NRF-2016R1A2B4009525, NRF-2015H1A2A1033613)
- Korea University
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- selenoprotein P, apolipoprotein E, exosomes, selenium homeostasis, blood-brain barrier, ApoER2, heparin-binding site, selenoprotein biosynthesis, amyloid-beta, neuronal cell death, ApoE-deficient mice
- MeSH terms
- Animals, Apolipoproteins E, Blood-Brain Barrier, Brain, Cell Line, Humans, Liver, Mice, Inbred C57BL, Amyloid beta-Peptides, Protein Transport, Hepatocytes, Endothelial Cells, Cell Line, Tumor, Selenoprotein P, Mice, Exosomes, Hep G2 Cells, HEK293 Cells
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