The recycling of apolipoprotein E in primary cultures of mouse hepatocytes

Evidence for a physiologic connection to high density lipoprotein metabolism

Monica H. Farkas, Larry L. Swift, Alyssa H. Hasty, MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Internalization of apoE-containing very low density protein (VLDL) by hepatocytes in vivo and in vitro leads to apoE recycling and resecretion. Because of the role of apoE in VLDL metabolism, apoE recycling may influence lipoprotein assembly or remnant uptake. However, apoE is also a HDL protein, and apoE recycling may be related to reverse cholesterol transport. To investigate apoE recycling, apoE-/- mouse hepatocytes were incubated (pulsed) with wild-type mouse lipoproteins, and cells and media were collected at chase periods up to 24 h. When cells were pulsed with VLDL, apoE was resecreted within 30 min. Although the mass of apoE in the media decreased with time, it could be detected up to 24 h after the pulse. Intact intracellular apoE was also detectable 24 h after the pulse. ApoE was also resecreted when cells were pulsed with HDL. When apoA-I 1 was included in the chase media after a pulse with VLDL, apoE resecretion increased 4-fold. Furthermore, human apoE was resecreted from wild-type mouse hepatocytes after a pulse with human VLDL. Finally, apoE was resecreted from mouse peritoneal macrophages after pulsing with VLDL. We conclude that 1) HDL apoE recycles in a quantitatively comparable fashion to VLDL apoE; 2) apoE recycling can be modulated by extracellular apoA-I but is not affected by endogenous apoE; and 3) recycling occurs in macrophages as well as in hepatocytes, suggesting that the process is not cell-specific.

Original languageEnglish (US)
Pages (from-to)9412-9417
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number11
DOIs
StatePublished - Mar 14 2003
Externally publishedYes

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Recycling
Apolipoproteins E
HDL Lipoproteins
Metabolism
Hepatocytes
Apolipoprotein A-I
Macrophages
Lipoproteins
Peritoneal Macrophages

ASJC Scopus subject areas

  • Biochemistry

Cite this

The recycling of apolipoprotein E in primary cultures of mouse hepatocytes : Evidence for a physiologic connection to high density lipoprotein metabolism. / Farkas, Monica H.; Swift, Larry L.; Hasty, Alyssa H.; Linton, MacRae F.; Fazio, Sergio.

In: Journal of Biological Chemistry, Vol. 278, No. 11, 14.03.2003, p. 9412-9417.

Research output: Contribution to journalArticle

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