(Hypertension. 1997;30:1389-1396.)
© 1997 American Heart Association, Inc.
Articles |
Mannose 6-Phosphate Receptor–Mediated Internalization and Activation of Prorenin by Cardiac Cells
From the Cardiovascular Research Institute COEUR, Departments of Pharmacology (C.A.M. van K., A.H.J.D., P.R.S), Biochemistry (D.H.W.D., J.M.J.L.), and Internal Medicine I (C.A.M. van K., F.H.M.D., M.A.D.H.S.), Erasmus University Rotterdam, Rotterdam, The Netherlands.
Correspondence to A.H.J. Danser, PhD, Department of Pharmacology, Room EE1418b, Erasmus University, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands. E-mail danser{at}farma.fgg.eur.nl
Abstract The binding and internalization of recombinant human renin and prorenin (2500 µU/mL) and the activation of prorenin were studied in neonatal rat cardiac myocytes and fibroblasts cultured in a chemically defined medium. Surface-bound and internalized enzymes were distinguished by the addition of mannose 6-phosphate to the medium, by incubating the cells both at 37°C and 4°C, and by the acid-wash method. Mannose 6-phosphate inhibited the binding of renin and prorenin to the myocyte cell surface in a dose-dependent manner. At 37°C, after incubation at 4°C for 2 hours, 60% to 70% of cell surface-bound renin or prorenin was internalized within 5 minutes. Intracellular prorenin was activated, but extracellular prorenin was not. The half-time of activation at 37°C was 25 minutes. Ammonium chloride and monensin, which interfere with the normal trafficking and recycling of internalized receptors and ligands, inhibited the activation of prorenin. Results obtained with cardiac fibroblasts were comparable to those in the myocytes. This study is the first to show experimental evidence for the internalization and activation of prorenin in extrarenal cells by a mannose 6-phosphate receptor–dependent process. Our findings may have physiological significance in light of recent experimental data indicating that angiotensin I and II are produced at cardiac and other extrarenal tissue sites by the action of renal renin and that intracellular angiotensin II can elicit important physiological responses.
Key Words: endocytosis • fibroblasts • myocytes • heart • renin
This article has been cited by other articles:
 |
|
 |
|
  M. Krop, R. van Veghel, I. M. Garrelds, R. J.A. de Bruin, J. M.G. van Gool, A. H. van den Meiracker, M. Thio, P. L.A. van Daele, and A.H. J. Danser Cardiac Renin Levels Are Not Influenced by the Amount of Resident Mast Cells Hypertension, August 1, 2009; 54(2): 315 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. P. Singh, B. Le, R. Khode, K. M. Baker, and R. Kumar Intracellular Angiotensin II Production in Diabetic Rats Is Correlated With Cardiomyocyte Apoptosis, Oxidative Stress, and Cardiac Fibrosis Diabetes, December 1, 2008; 57(12): 3297 - 3306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M Dahms, L. J Olson, and J.-J. P Kim Strategies for carbohydrate recognition by the mannose 6-phosphate receptors Glycobiology, September 1, 2008; 18(9): 664 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. W. Batenburg, R. J.A. de Bruin, J. M.G. van Gool, D. N. Muller, M. Bader, G. Nguyen, and A. H. J. Danser Aliskiren-Binding Increases the Half Life of Renin and Prorenin in Rat Aortic Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1151 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J.V. McMurray, B. Pitt, R. Latini, A. P. Maggioni, S. D. Solomon, D. L. Keefe, J. Ford, A. Verma, J. Lewsey, and for the Aliskiren Observation of Heart Failure Tre Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nguyen and A. H. J. Danser Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents Exp Physiol, May 1, 2008; 93(5): 557 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Feldt, U. Maschke, R. Dechend, F. C. Luft, and D. N. Muller The Putative (Pro)renin Receptor Blocker HRP Fails to Prevent (Pro)renin Signaling J. Am. Soc. Nephrol., April 1, 2008; 19(4): 743 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Feldt, W. W. Batenburg, I. Mazak, U. Maschke, M. Wellner, H. Kvakan, R. Dechend, A. Fiebeler, C. Burckle, A. Contrepas, et al. Prorenin and Renin-Induced Extracellular Signal-Regulated Kinase 1/2 Activation in Monocytes Is Not Blocked by Aliskiren or the Handle-Region Peptide Hypertension, March 1, 2008; 51(3): 682 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Muller, B. Klanke, S. Feldt, N. Cordasic, A. Hartner, R. E. Schmieder, F. C. Luft, and K. F. Hilgers (Pro)Renin Receptor Peptide Inhibitor "Handle-Region" Peptide Does Not Affect Hypertensive Nephrosclerosis in Goldblatt Rats Hypertension, March 1, 2008; 51(3): 676 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Schweda, U. Friis, C. Wagner, O. Skott, and A. Kurtz Renin Release Physiology, October 1, 2007; 22(5): 310 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Whaley-Connell, G. Govindarajan, J. Habibi, M. R. Hayden, S. A. Cooper, Y. Wei, L. Ma, M. Qazi, D. Link, P. R. Karuparthi, et al. Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E355 - E363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Jan Danser, W. W. Batenburg, and J. H. M. van Esch Prorenin and the (pro)renin receptor--an update Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1288 - 1292. [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, Y. Kaneshiro, T. Takemitsu, M. Sakoda, T. Nakagawa, A. Nishiyama, H. Kawachi, F. Shimizu, and T. Inagami Contribution of Nonproteolytically Activated Prorenin in Glomeruli to Hypertensive Renal Damage J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2495 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, Y. Kaneshiro, T. Takemitsu, M. Sakoda, F. Suzuki, T. Nakagawa, A. Nishiyama, T. Inagami, and M. Hayashi Nonproteolytic Activation of Prorenin Contributes to Development of Cardiac Fibrosis in Genetic Hypertension Hypertension, May 1, 2006; 47(5): 894 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.H. J. Danser and J. Deinum Renin, Prorenin and the Putative (Pro)renin Receptor Hypertension, November 1, 2005; 46(5): 1069 - 1076. [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Danser and J. Deinum Spotlight on Renin: Renin, Prorenin and the Putative (Pro)renin Receptor Journal of Renin-Angiotensin-Aldosterone System, September 1, 2005; 6(3): 163 - 165. [PDF]
|
|
|
|
 |
|
 F. C. Luft Cardiac Angiotensin Is Upregulated in the Hearts of Unstable Angina Patients Circ. Res., June 25, 2004; 94(12): 1530 - 1532. [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Carey and H. M. Siragy Newly Recognized Components of the Renin-Angiotensin System: Potential Roles in Cardiovascular and Renal Regulation Endocr. Rev., June 1, 2003; 24(3): 261 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Peters, R. Farrenkopf, S. Clausmeyer, J. Zimmer, S. Kantachuvesiri, M. G.F. Sharp, and J. J. Mullins Functional Significance of Prorenin Internalization in the Rat Heart Circ. Res., May 31, 2002; 90(10): 1135 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Hancock, D. J. Haskins, G. Sun, and N. M. Dahms Identification of Residues Essential for Carbohydrate Recognition by the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor J. Biol. Chem., March 22, 2002; 277(13): 11255 - 11264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Saris, M. M.E.D. van den Eijnden, J. M.J. Lamers, P. R. Saxena, M. A.D.H. Schalekamp, and A.H. J. Danser Prorenin-Induced Myocyte Proliferation: No Role for Intracellular Angiotensin II Hypertension, February 1, 2002; 39(2): 573 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Deinum, J. M.G. van Gool, M. J.M. Kofflard, F. J. ten Cate, and A.H. J. Danser Angiotensin II Type 2 Receptors and Cardiac Hypertrophy in Women With Hypertrophic Cardiomyopathy Hypertension, December 1, 2001; 38(6): 1278 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. E. D. van den Eijnden, J. J. Saris, R. J. A. de Bruin, E. de Wit, W. Sluiter, T. L. Reudelhuber, M. A. D. H. Schalekamp, F. H. M. Derkx, and A. H. J. Danser Prorenin Accumulation and Activation in Human Endothelial Cells : Importance of Mannose 6-Phosphate Receptors Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 911 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Saris, F. H. M. Derkx, R. J. A. De Bruin, D. H. W. Dekkers, J. M. J. Lamers, P. R. Saxena, M. A. D. H. Schalekamp, and A. H. Jan Danser High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1706 - H1715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Saris, F. H. M. Derkx, J. M. J. Lamers, P. R. Saxena, M. A. D. H. Schalekamp, and A. H. J. Danser Cardiomyocytes Bind and Activate Native Human Prorenin : Role of Soluble Mannose 6-Phosphate Receptors Hypertension, February 1, 2001; 37(2): 710 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Clausmeyer, A. Reinecke, R. Farrenkopf, T. Unger, and J. Peters Tissue-Specific Expression of a Rat Renin Transcript Lacking the Coding Sequence for the Prefragment and Its Stimulation by Myocardial Infarction Endocrinology, August 1, 2000; 141(8): 2963 - 2970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. De Mello and A. H. J. Danser Angiotensin II and the Heart : On the Intracrine Renin-Angiotensin System Hypertension, June 1, 2000; 35(6): 1183 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Almeida, V. Oliveira, J. R. Chagas, M. Meldal, M. A. Juliano, and L. Juliano Hydrolysis by Cathepsin B of Fluorescent Peptides Derived From Human Prorenin Hypertension, June 1, 2000; 35(6): 1278 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.H.J. Danser, J. J Saris, M. P Schuijt, and J. P van Kats Is there a local renin--angiotensin system in the heart? Cardiovasc Res, November 1, 1999; 44(2): 252 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Dostal and K. M. Baker The Cardiac Renin-Angiotensin System : Conceptual, or a Regulator of Cardiac Function? Circ. Res., October 1, 1999; 85(7): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A.M van Kesteren, J. J Saris, D. H.W Dekkers, J. M.J Lamers, P. R Saxena, M. A.D.H Schalekamp, and A.H.J. Danser Cultured neonatal rat cardiac myocytes and fibroblasts do not synthesize renin or angiotensinogen: evidence for stretch-induced cardiomyocyte hypertrophy independent of angiotensin II Cardiovasc Res, July 1, 1999; 43(1): 148 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Muller, K. F. Hilgers, S. Mathews, V. Breu, W. Fischli, R. Uhlmann, and F. C. Luft Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen Hypertension, January 1, 1999; 33(1): 312 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. R. M. Osterop, M. J. M. Kofflard, L. A. Sandkuijl, F. J. t. Cate, R. Krams, M. A. D. H. Schalekamp, and A. H. J. Danser AT1 Receptor A/C1166 Polymorphism Contributes to Cardiac Hypertrophy in Subjects With Hypertrophic Cardiomyopathy Hypertension, November 1, 1998; 32(5): 825 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. de Lannoy, A.H. J. Danser, A. M.B. Bouhuizen, P. R. Saxena, and M. A.D.H. Schalekamp Localization and Production of Angiotensin II in the Isolated Perfused Rat Heart Hypertension, May 1, 1998; 31(5): 1111 - 1117. [Abstract] [Full Text] [PDF]
|
|