Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1

Pan X, Grigoryeva L, Seyrantepe V, Peng J, Kollmann K, Tremblay J, Lavoie JL, Hinek A, Lübke T, Pshezhetsky AV (2014)
PLoS genetics 10(2).

Download
OA
Journal Article | Published | English
Author
; ; ; ; ; ; ; ; ;
Abstract
The potent vasoconstrictor peptides, endothelin 1 (ET-1) and angiotensin II control adaptation of blood vessels to fluctuations of blood pressure. Previously we have shown that the circulating level of ET-1 is regulated through its proteolytic cleavage by secreted serine carboxypeptidase, cathepsin A (CathA). However, genetically-modified mouse expressing catalytically inactive CathA S190A mutant retained about 10-15% of the carboxypeptidase activity against ET-1 in its tissues suggesting a presence of parallel/redundant catabolic pathway(s). In the current work we provide direct evidence that the enzyme, which complements CathA action towards ET-1 is a retinoid-inducible lysosomal serine carboxypeptidase 1 (Scpep1), a CathA homolog with previously unknown biological function. We generated a mouse strain devoid of both CathA and Scpep1 activities (DD mice) and found that in response to high-salt diet and systemic injections of ET-1 these animals showed significantly increased blood pressure as compared to wild type mice or those with single deficiencies of CathA or Scpep1. We also found that the reactivity of mesenteric arteries from DD mice towards ET-1 was significantly higher than that for all other groups of mice. The DD mice had a reduced degradation rate of ET-1 in the blood whereas their cultured arterial vascular smooth muscle cells showed increased ET-1-dependent phosphorylation of myosin light chain 2. Together, our results define the biological role of mammalian serine carboxypeptidase Scpep1 and suggest that Scpep1 and CathA together participate in the control of ET-1 regulation of vascular tone and hemodynamics.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Pan X, Grigoryeva L, Seyrantepe V, et al. Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS genetics. 2014;10(2).
Pan, X., Grigoryeva, L., Seyrantepe, V., Peng, J., Kollmann, K., Tremblay, J., Lavoie, J. L., et al. (2014). Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS genetics, 10(2).
Pan, X., Grigoryeva, L., Seyrantepe, V., Peng, J., Kollmann, K., Tremblay, J., Lavoie, J. L., Hinek, A., Lübke, T., and Pshezhetsky, A. V. (2014). Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS genetics 10.
Pan, X., et al., 2014. Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS genetics, 10(2).
X. Pan, et al., “Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1”, PLoS genetics, vol. 10, 2014.
Pan, X., Grigoryeva, L., Seyrantepe, V., Peng, J., Kollmann, K., Tremblay, J., Lavoie, J.L., Hinek, A., Lübke, T., Pshezhetsky, A.V.: Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS genetics. 10, (2014).
Pan, Xuefang, Grigoryeva, Lubov, Seyrantepe, Volkan, Peng, Junzheng, Kollmann, Katrin, Tremblay, Johanne, Lavoie, Julie L., Hinek, Aleksander, Lübke, Torben, and Pshezhetsky, Alexey V. “Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1”. PLoS genetics 10.2 (2014).
Main File(s)
Access Level
OA Open Access
Last Uploaded
2014-04-23 10:37:48

This data publication is cited in the following publications:
This publication cites the following data publications:

1 Citation in Europe PMC

Data provided by Europe PubMed Central.

40 References

Data provided by Europe PubMed Central.

Identification of novel lysosomal matrix proteins by proteome analysis.
Kollmann K, Mutenda KE, Balleininger M, Eckermann E, von Figura K, Schmidt B, Lubke T., Proteomics 5(15), 2005
PMID: 16145712
The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase.
Hinek A, Rabinovitch M, Keeley F, Okamura-Oho Y, Callahan J., J. Clin. Invest. 91(3), 1993
PMID: 8383699
Novel β-amino acid derivatives as inhibitors of cathepsin A.
Ruf S, Buning C, Schreuder H, Horstick G, Linz W, Olpp T, Pernerstorfer J, Hiss K, Kroll K, Kannt A, Kohlmann M, Linz D, Hubschle T, Rutten H, Wirth K, Schmidt T, Sadowski T., J. Med. Chem. 55(17), 2012
PMID: 22861813
Infantile galactosialidosis presenting with congenital adrenal hyperplasia and renal hypertension.
Kyllerman M, Mansson JE, Westphal O, Conradi N, Nellstrom H., Pediatr. Neurol. 9(4), 1993
PMID: 8216548
Retinoids and pulmonary hypertension.
Preston IR, Tang G, Tilan JU, Hill NS, Suzuki YJ., Circulation 111(6), 2005
PMID: 15699255
Effect of all-trans-retinoic acid on the development of chronic hypoxia-induced pulmonary hypertension.
Zhang E, Jiang B, Yokochi A, Maruyama J, Mitani Y, Ma N, Maruyama K., Circ. J. 74(8), 2010
PMID: 20606328
Retinoic acid rescues alveolar hypoplasia in the calorie-restricted developing rat lung.
Londhe VA, Maisonet TM, Lopez B, Shin BC, Huynh J, Devaskar SU., Am. J. Respir. Cell Mol. Biol. 48(2), 2013
PMID: 23087051
Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule.
Lavoie JL, Lake-Bruse KD, Sigmund CD., Am. J. Physiol. Renal Physiol. 286(5), 2004
PMID: 15075192
Development of hypertension and kidney hypertrophy in transgenic mice overexpressing ARAP1 gene in the kidney.
Guo DF, Chenier I, Lavoie JL, Chan JS, Hamet P, Tremblay J, Chen XM, Wang DH, Inagami T., Hypertension 48(3), 2006
PMID: 16801480
Impact of diet and stress on the development of preeclampsia-like symptoms in p57kip2 mice.
Falcao S, Solomon C, Monat C, Berube J, Gutkowska J, Lavoie JL., Am. J. Physiol. Heart Circ. Physiol. 296(1), 2009
PMID: 18978188
Exercise training can attenuate preeclampsia-like features in an animal model.
Falcao S, Bisotto S, Michel C, Lacasse AA, Vaillancourt C, Gutkowska J, Lavoie JL., J. Hypertens. 28(12), 2010
PMID: 20811291

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 24586188
PubMed | Europe PMC

Search this title in

Google Scholar