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Determinants of human apolipoprotein [a] secretion from mouse hepatocyte cultures

Record type: Article

Efforts to develop an in vitro model system to analyze apolipoprotein [a] (apo[a]) gene transcription, mRNA translation, and protein secretion have been complicated by the limited tissue and species distribution of apo[a] and the presence of regulatory DNA sequences remote from the apo[a] transcription start site. In the current study we examined primary hepatocytes cultured from apo[a] transgenic mice as a model system for analyzing apo[a] biogenesis. Hepatocytes from mice transgenic for a yeast artificial chromosome (YAC) encoding the entire apo[a] gene in its own genomic context (YAC-apo[a] hepatocytes) were unable to maintain apo[a] expression beyond 48 h of culture. This suggests that the apo[a] promoter was not active in cultured YAC-apo[a] hepatocytes. In contrast, apo[a] expression was maintained for at least 7 days in hepatocytes cultured from mice transgenic for an apo[a] cDNA under control of the mouse transferrin promoter (transferrin-apo[a] hepatocytes). Pulse-chase experiments established that more than 80% of apo[a] synthesized by both transferrin-apo[a] and YAC-apo[a] hepatocytes was degraded prior to secretion, independently of the coexpression of human apoB.
Thus, low secretion efficiency appears to be a general characteristic of human apo[a] proteins in mouse liver. Apo[a] secretion was increased somewhat (from 18% to 32%) in the presence of lipoprotein-containing serum. Transformed cell lines derived from transferrin apo[a] hepatocytes retained characteristics of apo[a] secretion similar to those observed in primary cells. Primary and transformed apo[a] transgenic hepatocytes may provide valuable additional models with which to study posttranslational mechanisms regulating apo[a] secretion

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Citation

Wang, Jim, Boedeker, Jennifer, Hobbs, Helen H. and White, Ann L. (2001) Determinants of human apolipoprotein [a] secretion from mouse hepatocyte cultures Journal of Lipid Research, 42, (1), pp. 60-69.

More information

Published date: 2001
Keywords: apolipoprotein B, endoplasmic reticulum, lipoprotein [a], proteasome, transcription, transformed liver cell lines

Identifiers

Local EPrints ID: 26654
URI: http://eprints.soton.ac.uk/id/eprint/26654
ISSN: 0022-2275
PURE UUID: d3df380e-ffb7-49dd-aa6e-173f9e19a48a

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 17 Jul 2017 16:06

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Contributors

Author: Jim Wang
Author: Jennifer Boedeker
Author: Helen H. Hobbs
Author: Ann L. White

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