Elevated synthesis of human alpha 1-antitrypsin hinders the secretion of murine alpha 1-antitrypsin from hepatocytes of transgenic mice.

R. N. Sifers, B. B. Rogers, H. K. Hawkins, M. J. Finegold, S. L. Woo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

alpha 1-Antitrypsin (AAT) is a major hepatic secretory protein. The elevated synthesis of human AAT within hepatocytes of transgenic mice results in its accumulation within a subset of distended cisternae of the rough endoplasmic reticulum. The protein does not accumulate in large insoluble aggregates as is the case for the human PiZ AAT variant. Furthermore, the accumulated protein is not associated with immunoglobulin heavy chain binding protein. Transgenic animals exhibiting an elevated synthesis and subsequent intrahepatic accumulation of human AAT exhibit reduced serum levels of murine AAT as a result of its hindered secretion and accumulation within the rough endoplasmic reticulum. Interestingly, the secretion of murine transferrin and albumin which represent glycosylated and non-glycosylated hepatic secretory proteins, respectively, is unaffected. Overall, these results demonstrate that the elevated synthesis of human AAT can hinder the export of murine AAT from the hepatic rough endoplasmic reticulum in an apparently specific manner.

Original languageEnglish (US)
Pages (from-to)15696-15700
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number26
StatePublished - Sep 15 1989
Externally publishedYes

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alpha 1-Antitrypsin
Transgenic Mice
Hepatocytes
Rough Endoplasmic Reticulum
Liver
Proteins
Genetically Modified Animals
Transferrin
Albumins
Animals
Serum

ASJC Scopus subject areas

  • Biochemistry

Cite this

Elevated synthesis of human alpha 1-antitrypsin hinders the secretion of murine alpha 1-antitrypsin from hepatocytes of transgenic mice. / Sifers, R. N.; Rogers, B. B.; Hawkins, H. K.; Finegold, M. J.; Woo, S. L.

In: Journal of Biological Chemistry, Vol. 264, No. 26, 15.09.1989, p. 15696-15700.

Research output: Contribution to journalArticle

Sifers, R. N. ; Rogers, B. B. ; Hawkins, H. K. ; Finegold, M. J. ; Woo, S. L. / Elevated synthesis of human alpha 1-antitrypsin hinders the secretion of murine alpha 1-antitrypsin from hepatocytes of transgenic mice. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 26. pp. 15696-15700.
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