Normal Blood Pressure and Plasma Renin Activity in Mice Lacking the Renin-binding Protein, a Cellular Renin Inhibitor

Schmitz, Christian; Gotthardt, Michael; Hinderlich, Stephan; Leheste, Jörg-Robert; Groß, Volkmar; Vorum, Henrik; Christensen, Erik; Luft, Friedrich C.; Takahashi, Saori; Willnow, Thomas E.

doi:10.1074/jbc.275.20.15357

Cited by 51 publications

(28 citation statements)

References 19 publications

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“…50 Moreover, the same authors suggested a regulation of RnBP gene expression by oestradiol, and the intravenous injection of the RnBP into rats resulted in a rapid and strong inhibition of plasma renin activity that persisted for at least 2 h. However, knockout of the gene encoding for this protein in mice did not show any effect on RAS activity or blood pressure. 51 Therefore, more studies are necessary to understand the role of RnBP in the control of ovarian renin activity and AngII production.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II profile and mRNA encoding RAS proteins during bovine follicular wave

Ferreira

Gasperin

Santos

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Angiotensin II (AngII) has a role in ovarian follicle development, ovulation, and oocyte meiotic resumption. The objective of the present study was to characterise the AngII profile and the mRNA encoding RAS proteins in a bovine follicular wave. Cows were ovariectomised when the size between the largest (F1) and the second largest follicle (F2) was not statistically different (day 2), slightly different (day 3), or markedly different (day 4). AngII was measured in the follicular fluid and the mRNA abundance of genes encoding angiotensin-converting enzyme (ACE), (pro)renin receptor, and reninbinding protein (RnBP) was evaluated in the follicular cells from F1 and F2. The AngII levels increased at the expected time of the follicular deviation in F1 but did not change in F2. However, the expression of the genes encoding ACE, (pro)renin receptor, and RnBP was not regulated in F1 but was upregulated during or after the follicular deviation in F2. Moreover, RnBP gene expression increased when the F1 was treated with the oestrogen receptor-antagonist in vivo. In conclusion, the AngII concentration increased in the follicular fluid of the dominant follicle during and after deviation and further supports our finding that RAS is present in the ovary regulating follicular dominance.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II profile and mRNA encoding RAS proteins during bovine follicular wave

Ferreira

Gasperin

Santos

et al. 2011

J Renin Angiotensin Aldosterone Syst

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show abstract

“…72 Mice lacking RnBP display normal blood pressure and plasma renin activity. 73 Therefore, it is unlikely that this intracellular RnBP is a determinant of renin activity and/or metabolism in vivo.…”

Section: (Pro)renin Receptorsmentioning

confidence: 99%

Renin, Prorenin and the Putative (Pro)renin Receptor

2005

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“…9,23,24 One renin-binding protein identified in tissue homogenates is identical to N-acyl-D-glucosamine-2-epimerase, a cytosolic protein that inhibits renin in vitro but is not considered to participate in the RAS in vivo. 25 The M6P/insulin-like growth factor II receptor binds renin and prorenin with a K d of Ϸ1 nmol/L. 9 This receptor binds only glycosylated proteins with M6P residues.…”

Section: Renin-binding Proteinsmentioning

confidence: 99%

Critical Review of Prorenin and (Pro)renin Receptor Research

Campbell

2008

Hypertension

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T he renin-angiotensin system (RAS) plays an important role in cardiovascular and renal physiology and disease, and the benefits of angiotensin-converting enzyme inhibitor, angiotensin type 1 receptor blocker, and renin inhibitor therapies are mediated in part by their modification of the levels and actions of angiotensin peptides. Despite its long history, the RAS remains an active area of research. Contrary to the classical view of the RAS as an endocrine system whereby kidney-secreted renin acts on circulating angiotensinogen to produce angiotensin peptides in the circulation, it is now recognized that tissues are the main sites of angiotensin peptide formation by the action of plasma-(kidney-) derived renin on plasma-derived and locally synthesized angiotensinogen. 1-3 A receptor for prorenin and renin was recently identified 4,5 that is hereby referred to as the (pro)renin receptor. Prorenin and (pro)renin receptor research offers the exciting possibility of a new paradigm for the RAS whereby renin and prorenin binding to the (pro)renin receptor not only target and facilitate angiotensin generation but also lead to activation of (pro)renin receptor signal transduction pathways distinct from angiotensin II receptor signals. 6,7 By revealing novel potential mechanisms of disease pathogenesis, this new paradigm offers the possibility of new therapies that may be more effective than those currently available. It also suggests that stimulation of the (pro)renin receptor by the increased renin and prorenin levels that accompany angiotensin-converting enzyme inhibitor, angiotensin type 1 receptor blocker, and renin inhibitor therapies may attenuate the benefits these therapies. 7,8 Recent reviews and editorials have discussed this research. 6,9,10 The purpose of this brief review is to critically assess the evidence for this new paradigm from the perspective of disease pathogenesis and to advocate caution in its interpretation. The available evidence presents contradictions and difficulties of interpretation that preclude any conclusion about the reality of this new paradigm. Renin and ProreninRenin is an aspartyl protease synthesized as an inactive zymogen, prorenin. 11 Renin has a bilobed structure, with each lobe contributing 1 of the 2 essential aspartyl residues of its active site. 12 Prorenin has an amino-terminal prosequence that is thought to fold over the cleft between the 2 lobes of the enzyme, thereby preventing access to the active site by its substrate, angiotensinogen. Pure prorenin has a low intrinsic activity of Ͻ3% of the activity of fully activated prorenin, and this intrinsic activity is attributed to partial unfolding of the prosegment. 13,14 Human renin and prorenin are glycosylated, and a variable proportion of renin and prorenin has mannose-6-phosphate (M6P) residues and binds to the M6P-insulin-like growth factor II receptor. 9 Basal renin levels are Ͻ1 pmol/L in humans, and prorenin levels are Ϸ10-fold higher than renin levels (Table S1, available online at http://hyper.ahajournals.org).Re...

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Normal Blood Pressure and Plasma Renin Activity in Mice Lacking the Renin-binding Protein, a Cellular Renin Inhibitor

Cited by 51 publications

References 19 publications

Angiotensin II profile and mRNA encoding RAS proteins during bovine follicular wave

Angiotensin II profile and mRNA encoding RAS proteins during bovine follicular wave

Renin, Prorenin and the Putative (Pro)renin Receptor

Critical Review of Prorenin and (Pro)renin Receptor Research

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