Determinants of human apolipoprotein [a] secretion from mouse hepatocyte cultures
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), 60-69.
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Description/Abstract
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
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Keywords: | apolipoprotein B, endoplasmic reticulum, lipoprotein [a], proteasome, transcription, transformed liver cell lines |
| Subjects: | Q Science > Q Science (General) R Medicine > R Medicine (General) |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 26654 |
| Date Deposited: | 24 Apr 2006 |
| Last Modified: | 01 Jun 2011 14:02 |
| Contributors: | Wang, Jim (Author) Boedeker, Jennifer (Author) Hobbs, Helen H. (Author) White, Ann L. (Author) |
| Date: | 2001 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/26654 |
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