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Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion

Record type: Article

Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by ~70%, but by only ~45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin.
In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

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Citation

Boedeker, Jennifer C., Doolittle, Mark H. and White, Ann L. (2001) Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion Journal of Lipid Research, 42, (11), pp. 1858-1864.

More information

Published date: 2001
Keywords: calnexin, castanospermine, endoplasmic reticulum, fetal hepatocytes, glucosidase enzymes

Identifiers

Local EPrints ID: 26222
URI: http://eprints.soton.ac.uk/id/eprint/26222
ISSN: 0022-2275
PURE UUID: 4d6f8ca3-5a75-4b5c-bd6c-3f4000ec807d

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 17 Jul 2017 16:08

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Contributors

Author: Jennifer C. Boedeker
Author: Mark H. Doolittle
Author: Ann L. White

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