Cathepsin B is not the processing enzyme for mouse prorenin

Chantal Mercure, Marie Josée Lacombe, Khashayarsha Khazaie, Timothy L. Reudelhuber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Cathepsin B
Renin
Kidney
Renin-Angiotensin System
prorenin processing enzyme
Aspartic Acid Proteases
Chloroquine
Enzymes
Peptide Hydrolases
Cell Culture Techniques
Molecular Weight

Keywords

  • Blood pressure
  • Enzyme precursor
  • Mouse knock out
  • Renin
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Cathepsin B is not the processing enzyme for mouse prorenin. / Mercure, Chantal; Lacombe, Marie Josée; Khazaie, Khashayarsha; Reudelhuber, Timothy L.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 298, No. 5, 05.2010.

Research output: Contribution to journalArticle

@article{9353ad1b4d734aceac55d729a6c269e9,
title = "Cathepsin B is not the processing enzyme for mouse prorenin",
abstract = "Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.",
keywords = "Blood pressure, Enzyme precursor, Mouse knock out, Renin, Renin-angiotensin system",
author = "Chantal Mercure and Lacombe, {Marie Jos{\'e}e} and Khashayarsha Khazaie and Reudelhuber, {Timothy L.}",
year = "2010",
month = "5",
doi = "10.1152/ajpregu.00830.2009",
language = "English (US)",
volume = "298",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Cathepsin B is not the processing enzyme for mouse prorenin

AU - Mercure, Chantal

AU - Lacombe, Marie Josée

AU - Khazaie, Khashayarsha

AU - Reudelhuber, Timothy L.

PY - 2010/5

Y1 - 2010/5

N2 - Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.

AB - Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.

KW - Blood pressure

KW - Enzyme precursor

KW - Mouse knock out

KW - Renin

KW - Renin-angiotensin system

UR - http://www.scopus.com/inward/record.url?scp=77951739052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951739052&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00830.2009

DO - 10.1152/ajpregu.00830.2009

M3 - Article

C2 - 20164204

AN - SCOPUS:77951739052

VL - 298

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5

ER -