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2008 ; 12
(4
): 1229-37
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A renin transcript lacking exon 1 encodes for a non-secretory intracellular renin
that increases aldosterone production in transgenic rats
#MMPMID18782187
Peters J
; Wanka H
; Peters B
; Hoffmann S
J Cell Mol Med
2008[Aug]; 12
(4
): 1229-37
PMID18782187
show ga
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.