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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-9-10
pubmed:abstractText
Renin transcripts lacking exon 1 and thus the signal sequence for co-translational transport to the endoplasmatic reticulum encode for a protein (exon[2-9]renin), that is confined to the cytoplasm. The function of exon(2-9)renin is currently unknown. Mitochondrial renin increases under conditions which stimulate aldosterone production. We hypothesized that exon(2-9)renin (1) is translated into a functionally active protein in vivo, (2) is not secreted but remains within the cytoplasm and (3) stimulates aldosterone production. To test these hypotheses we generated transgenic rats overexpressing exon(2-9)renin. Four transgenic lines were obtained expressing the transcript in various tissues including the heart and the adrenal gland. Renin was enriched particularly in the cytoplasm of transgenic rats. Renin was not elevated in plasma, indicating that exon(2-9)renin is produced but not secreted. The ratio of aldosterone to renin concentrations in plasma (PAC/PRC) was elevated in all transgenic lines except line 307, which also did not exhibit elevated cytoplasmatic renin levels in the adrenal gland (PAC/PRC in controls: 2.8+/-2.3; line 307: 1.9+/-0.8; n. s.; line 284: 5.8+/-1.9; P<0.02; line 294: 5.0+/-2.3; P<0.001; line 276: 10.3+/-5.1; P<0.001). We conclude that the exon(1A-9) renin transcript (1) is translated into a functionally active intracellular protein; (2) is targeted to the cytoplasm rather than being sorted to the secretory pathways and (3) is functionally active, regulating aldosterone production. The CX-(exon2-9)renin transgenic rat appears to be a useful model to study the role and the mechanisms of action of cytoplasmatic renin derived from exon(1A-9) transcripts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1582-1838
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1229-37
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
A renin transcript lacking exon 1 encodes for a non-secretory intracellular renin that increases aldosterone production in transgenic rats.
pubmed:affiliation
Department of Cardiovascular Medicine, University of Greifswald, Greifswald, Germany. joerg.peters@uni-greifswald.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't