A Recycling Pathway for Resecretion of Internalized Apolipoprotein E in Liver Cells

Larry L. Swift, Monica H. Farkas, Amy S. Major, Klara Valyi-Nagy, MacRae F. Linton, Sergio Fazio

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Abstract

We have investigated the recycling of apoE in livers of apoE-/- mice transplanted with wild type bone marrow (apoE+/+ → apoE-/-), a model in which circulating apoE is derived exclusively from macrophages. Nascent Golgi lipoproteins were recovered from livers of apoE+/+ → apoE-/- mice 8 weeks after transplantation. ApoE was identified with nascent d <1.006 and with d 1.006-1.210 g/ml lipoproteins at a level ∼6% that of nascent lipoproteins from C57BL/6 mice. Hepatocytes from apoE+/+ → apoE-/- mice were isolated and cultured in media free of exogenous apoE. ApoE was found in the media primarily on the d <1.006 g/ml fraction, indicating a resecretion of internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was consistent with constitutive production, whereas the majority of apoE secreted from apoE+/+ → apoE-/- hepatocytes was recovered in the last 24 h of culture. This suggests that release may be triggered by accumulation of an acceptor, such as very low density lipoproteins, in the media. In agreement with the in vivo data, total recovery of apoE from apoE +/+ → apoE-/- hepatocytes was ∼6% that of the apoE recovered from C57BL/6 hepatocytes. Since plasma apoE levels in the transplanted mice are ∼10% of control levels, the findings indicate that up to 60% of the internalized apoE may be reutilized under physiologic conditions. These studies provide definitive evidence for the sparing of apoE and its routing through the secretory pathway and demonstrate that internalized apoE can be resecreted in a quantitatively significant fashion.

Original languageEnglish (US)
Pages (from-to)22965-22970
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
StatePublished - Jun 22 2001
Externally publishedYes

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Apolipoproteins E
Liver
Recycling
Hepatocytes
Lipoproteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

A Recycling Pathway for Resecretion of Internalized Apolipoprotein E in Liver Cells. / Swift, Larry L.; Farkas, Monica H.; Major, Amy S.; Valyi-Nagy, Klara; Linton, MacRae F.; Fazio, Sergio.

In: Journal of Biological Chemistry, Vol. 276, No. 25, 22.06.2001, p. 22965-22970.

Research output: Contribution to journalArticle

Swift, Larry L. ; Farkas, Monica H. ; Major, Amy S. ; Valyi-Nagy, Klara ; Linton, MacRae F. ; Fazio, Sergio. / A Recycling Pathway for Resecretion of Internalized Apolipoprotein E in Liver Cells. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 25. pp. 22965-22970.
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abstract = "We have investigated the recycling of apoE in livers of apoE-/- mice transplanted with wild type bone marrow (apoE+/+ → apoE-/-), a model in which circulating apoE is derived exclusively from macrophages. Nascent Golgi lipoproteins were recovered from livers of apoE+/+ → apoE-/- mice 8 weeks after transplantation. ApoE was identified with nascent d <1.006 and with d 1.006-1.210 g/ml lipoproteins at a level ∼6{\%} that of nascent lipoproteins from C57BL/6 mice. Hepatocytes from apoE+/+ → apoE-/- mice were isolated and cultured in media free of exogenous apoE. ApoE was found in the media primarily on the d <1.006 g/ml fraction, indicating a resecretion of internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was consistent with constitutive production, whereas the majority of apoE secreted from apoE+/+ → apoE-/- hepatocytes was recovered in the last 24 h of culture. This suggests that release may be triggered by accumulation of an acceptor, such as very low density lipoproteins, in the media. In agreement with the in vivo data, total recovery of apoE from apoE +/+ → apoE-/- hepatocytes was ∼6{\%} that of the apoE recovered from C57BL/6 hepatocytes. Since plasma apoE levels in the transplanted mice are ∼10{\%} of control levels, the findings indicate that up to 60{\%} of the internalized apoE may be reutilized under physiologic conditions. These studies provide definitive evidence for the sparing of apoE and its routing through the secretory pathway and demonstrate that internalized apoE can be resecreted in a quantitatively significant fashion.",
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N2 - We have investigated the recycling of apoE in livers of apoE-/- mice transplanted with wild type bone marrow (apoE+/+ → apoE-/-), a model in which circulating apoE is derived exclusively from macrophages. Nascent Golgi lipoproteins were recovered from livers of apoE+/+ → apoE-/- mice 8 weeks after transplantation. ApoE was identified with nascent d <1.006 and with d 1.006-1.210 g/ml lipoproteins at a level ∼6% that of nascent lipoproteins from C57BL/6 mice. Hepatocytes from apoE+/+ → apoE-/- mice were isolated and cultured in media free of exogenous apoE. ApoE was found in the media primarily on the d <1.006 g/ml fraction, indicating a resecretion of internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was consistent with constitutive production, whereas the majority of apoE secreted from apoE+/+ → apoE-/- hepatocytes was recovered in the last 24 h of culture. This suggests that release may be triggered by accumulation of an acceptor, such as very low density lipoproteins, in the media. In agreement with the in vivo data, total recovery of apoE from apoE +/+ → apoE-/- hepatocytes was ∼6% that of the apoE recovered from C57BL/6 hepatocytes. Since plasma apoE levels in the transplanted mice are ∼10% of control levels, the findings indicate that up to 60% of the internalized apoE may be reutilized under physiologic conditions. These studies provide definitive evidence for the sparing of apoE and its routing through the secretory pathway and demonstrate that internalized apoE can be resecreted in a quantitatively significant fashion.

AB - We have investigated the recycling of apoE in livers of apoE-/- mice transplanted with wild type bone marrow (apoE+/+ → apoE-/-), a model in which circulating apoE is derived exclusively from macrophages. Nascent Golgi lipoproteins were recovered from livers of apoE+/+ → apoE-/- mice 8 weeks after transplantation. ApoE was identified with nascent d <1.006 and with d 1.006-1.210 g/ml lipoproteins at a level ∼6% that of nascent lipoproteins from C57BL/6 mice. Hepatocytes from apoE+/+ → apoE-/- mice were isolated and cultured in media free of exogenous apoE. ApoE was found in the media primarily on the d <1.006 g/ml fraction, indicating a resecretion of internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was consistent with constitutive production, whereas the majority of apoE secreted from apoE+/+ → apoE-/- hepatocytes was recovered in the last 24 h of culture. This suggests that release may be triggered by accumulation of an acceptor, such as very low density lipoproteins, in the media. In agreement with the in vivo data, total recovery of apoE from apoE +/+ → apoE-/- hepatocytes was ∼6% that of the apoE recovered from C57BL/6 hepatocytes. Since plasma apoE levels in the transplanted mice are ∼10% of control levels, the findings indicate that up to 60% of the internalized apoE may be reutilized under physiologic conditions. These studies provide definitive evidence for the sparing of apoE and its routing through the secretory pathway and demonstrate that internalized apoE can be resecreted in a quantitatively significant fashion.

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