Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
|
pubmed:dateCreated |
1995-6-22
|
pubmed:abstractText |
1. The Brown Norway (B/N) Katholiek rat is a mutant strain of plasma kininogen deficiency. The plasma of B/N-Katholiek rats was shown to contain only 3-5% of high-molecular-weight and low-molecular-weight kininogens (HK and LK) of the normal level by specific RIA, and 30% of prekallikrein was detected by amidase activity. However, HK antigen in the liver microsomal fraction of B/N-Katholiek rats was about 60% of that of normal rats. 2. In this paper we compare and discuss synthesis and secretion of HK and LK by primary cultures of livers of deficient and normal rats. The deficient hepatocytes could synthesize HK and LK in the same way as normal cells but could not secrete mature forms of HK and LK in the medium. Examination of the subcellular localization of the mutant HK in the hepatocytes showed that a larger amount of mutant HK antigen, compared to normal rats, was found in the 10,000 g fraction, which is rich in lysosomes, suggesting that the mutant HK may be transported to the lysosomes. 3. We also analyzed sequence of the HK cDNA of B/N-Katholiek and B/N-Kitasato rats and found a point mutation of G to A at nucleotide 487, which locates at the heavy chain region of HK and LK. 4. We constructed five expression plasmids to transfect COS-1 cells to examine HK secretion. COS-1 cells transfected with the plasmids containing the G to A transition could not secrete and retained HK, while those cells transfected with the plasmids containing normal G released HK into the medium. 5. These results indicate that a point mutation G to A at nucleotide 487, resulting in an amino acid transition from alanine (163) to threonine, is responsible for the defective secretion of HK and LK by the liver of B/N-Katholiek rats. We also discuss other cases of secretion defect of plasma proteins reported in the literature.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0100-879X
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
27
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1803-15
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:7749370-Animals,
pubmed-meshheading:7749370-DNA, Complementary,
pubmed-meshheading:7749370-Kininogens,
pubmed-meshheading:7749370-Liver,
pubmed-meshheading:7749370-Lysosomes,
pubmed-meshheading:7749370-Molecular Weight,
pubmed-meshheading:7749370-Plasmids,
pubmed-meshheading:7749370-Point Mutation,
pubmed-meshheading:7749370-Rats,
pubmed-meshheading:7749370-Rats, Inbred BN,
pubmed-meshheading:7749370-Transfection
|
pubmed:year |
1994
|
pubmed:articleTitle |
Molecular mechanism of kininogen deficiency in brown Norway Katholiek rats.
|
pubmed:affiliation |
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Review
|