Abstract |
The elongated mutant of alpha 2-plasmin inhibitor (alpha 2 PI) designated as alpha 2 PI-Nara is caused by a frameshift mutation found near the 3' end of the coding region of the alpha 2 PI gene. To elucidate the mechanism by which this molecular abnormality leads to alpha 2 PI deficiency in plasma, we transfected an expression plasmid for alpha 2 PI-Nara into a monkey kidney cell line COS-7 or human hepatoma cell line HepG2 synthesizing alpha 2 PI, and analyzed the secretory process of the expressed alpha 2 PI-Nara by radioimmunoprecipitation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. The results obtained showed that the recombinant alpha 2 PI-Nara was retained within the cells for prolonged periods as an endoglycosidase H-sensitive precursor form, and only a small portion of the recombinant protein was secreted into the medium as a neuraminidase-sensitive mature form. These results suggest that instead of being secreted from the cells, most of the alpha 2 PI-Nara undergoes degradation within the cells while its transport is retarded in the intracellular secretory pathway; thus, alpha 2 PI-Nara should lead to the alpha 2 PI deficiency primarily by causing a block in the intracellular transport from the endoplasmic reticulum to the Golgi complex.
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Authors | O Miura, N Aoki |
Journal | Blood
(Blood)
Vol. 75
Issue 5
Pg. 1092-6
(Mar 01 1990)
ISSN: 0006-4971 [Print] United States |
PMID | 1689597
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- alpha-Macroglobulins
- plasmin-alpha(2)-macroglobulin complex
- Hexosaminidases
- Neuraminidase
- Fibrinolysin
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Topics |
- Biological Transport
- Cell Line
- Cloning, Molecular
- Fibrinolysin
(deficiency, genetics, metabolism)
- Hexosaminidases
(metabolism)
- Humans
- Molecular Weight
- Neuraminidase
(metabolism)
- Tumor Cells, Cultured
- alpha-Macroglobulins
(deficiency, genetics, metabolism)
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