| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, Ottawa Hospital, Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada
2 Manitoba Centre for Proteomics, University of Manitoba, Winnipeg, Manitoba, Canada
* To whom correspondence should be addressed. E-mail: kburns{at}ottawahospital.on.ca.
Angiotensin converting enzyme 2 (ACE2) is a homologue of ACE, which is not blocked by conventional ACE inhibitors (ACEI). ACE2 converts angiotensin 1-10 (ANG I) to angiotensin 1-9 (ANG 1-9), which can be hydrolyzed by ACE to form the biologically active peptide angiotensin 1-7 (ANG 1-7). ACE2 is expressed in the kidney, but its precise intrarenal localization is unclear, and the role of intrarenal ACE2 in the production of ANG 1-7 is unknown. The present studies determined the relative distribution of ACE2 in the rat kidney, and defined its role in the generation of ANG 1-7 in proximal tubule. In microdissected rat nephron segments, semi-quantitative RT-PCR revealed that ACE2 mRNA was widely expressed, with relatively high levels in proximal straight tubule (PST). Immunohistochemistry demonstrated ACE2 protein in tubular segments, glomeruli, and endothelial cells. Utilizing mass spectrometry, incubation of isolated PSTs with ANG I (10-6 M) led to generation of ANG 1-7 (sensitivity of detection > 1 x 10-9 M), accompanied by the formation of angiotensin 1-8 (ANG II) and ANG 1-9. The ACE2 inhibitor DX600 completely blocked ANG I-mediated generation of ANG 1-7. Incubation of PSTs with ANG 1-9 also led to generation of ANG 1-7, an effect blocked by the ACEI captopril or enalaprilat, but not by DX600. Incubation of PSTs with ANG II or luminal perfusion of ANG II did not result in detection of ANG 1-7. The results indicate that ACE2 is widely expressed in rat nephron segments, and contributes to the production of ANG 1-7 from ANG I in PST. ANG II may not be a major substrate for ACE2 in isolated PST. The data suggest that ACE2-mediated production of ANG 1-7 represents an important component of the proximal tubular renin-angiotensin system.
This article has been cited by other articles:
|
|
 |
|
  C. B. Herath, J. S. Lubel, Z. Jia, E. Velkoska, D. Casley, L. Brown, C. Tikellis, L. M. Burrell, and P. W. Angus Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2 Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G98 - G106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gava, A. Samad-Zadeh, J. Zimpelmann, N. Bahramifarid, G. T. Kitten, R. A. Santos, R. M. Touyz, and K. D. Burns Angiotensin-(1-7) activates a tyrosine phosphatase and inhibits glucose-induced signalling in proximal tubular cells Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1766 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Q. Velez, K. J. Ryan, C. E. Harbeson, A. M. Bland, M. N. Budisavljevic, J. M. Arthur, W. R. Fitzgibbon, J. R. Raymond, and M. G. Janech Angiotensin I Is Largely Converted to Angiotensin (1-7) and Angiotensin (2-10) by Isolated Rat Glomeruli Hypertension, May 1, 2009; 53(5): 790 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Burns and N. Li Letter to the Editor Am J Physiol Renal Physiol, March 1, 2009; 296(3): F666 - F666. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Soler, M. Ye, J. Wysocki, J. William, J. Lloveras, and D. Batlle Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan Am J Physiol Renal Physiol, February 1, 2009; 296(2): F398 - F405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
CORRIGENDUM Am J Physiol Renal Physiol, September 1, 2008; 295(3): F857 - F857. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Soler, J. Wysocki, and D. Batlle Angiotensin-converting enzyme 2 and the kidney Exp Physiol, May 1, 2008; 93(5): 549 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Lara, J. S. Correa, A. B. Lavelle, A. G. Lopes, and C. Caruso-Neves The angiotensin receptor type 1-Gq protein-phosphatidyl inositol phospholipase C{beta}-protein kinase C pathway is involved in activation of proximal tubule Na+-ATPase activity by angiotensin(1-7) in pig kidneys Exp Physiol, May 1, 2008; 93(5): 639 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ji, S. Menini, W. Zheng, C. Pesce, X. Wu, and K. Sandberg Role of angiotensin-converting enzyme 2 and angiotensin(1-7) in 17{beta}-oestradiol regulation of renal pathology in renal wrap hypertension in rats Exp Physiol, May 1, 2008; 93(5): 648 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tikellis, K. Bialkowski, J. Pete, K. Sheehy, Q. Su, C. Johnston, M. E. Cooper, and M. C. Thomas ACE2 Deficiency Modifies Renoprotection Afforded by ACE Inhibition in Experimental Diabetes Diabetes, April 1, 2008; 57(4): 1018 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. A. Neves, K. Stovall, J. Joyner, G. Valdes, P. E. Gallagher, C. M. Ferrario, D. C. Merrill, and K. B. Brosnihan ACE2 and ANG-(1-7) in the rat uterus during early and late gestation Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R151 - R161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Ojeda, D. Grigore, E. B. Robertson, and B. T. Alexander Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring Hypertension, October 1, 2007; 50(4): 679 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Q. Velez, A. M. Bland, J. M. Arthur, J. R. Raymond, and M. G. Janech Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes Am J Physiol Renal Physiol, July 1, 2007; 293(1): F398 - F407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Keidar, M. Kaplan, and A. Gamliel-Lazarovich ACE2 of the heart: From angiotensin I to angiotensin (1-7) Cardiovasc Res, February 1, 2007; 73(3): 463 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Diez-Freire, J. Vazquez, M. F. Correa de Adjounian, M. F. R. Ferrari, L. Yuan, X. Silver, R. Torres, and M. K. Raizada ACE2 gene transfer attenuates hypertension-linked pathophysiological changes in the SHR Physiol Genomics, January 12, 2007; 27(1): 12 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Benter, M. H. M. Yousif, C. Cojocel, M. Al-Maghrebi, and D. I. Diz Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H666 - H672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Shaltout, B. M. Westwood, D. B. Averill, C. M. Ferrario, J. P. Figueroa, D. I. Diz, J. C. Rose, and M. C. Chappell Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II Am J Physiol Renal Physiol, January 1, 2007; 292(1): F82 - F91. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ye, J. Wysocki, J. William, M. J. Soler, I. Cokic, and D. Batlle Glomerular Localization and Expression of Angiotensin-Converting Enzyme 2 and Angiotensin-Converting Enzyme: Implications for Albuminuria in Diabetes J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3067 - 3075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Pendergrass, D. B. Averill, C. M. Ferrario, D. I. Diz, and M. C. Chappell Differential expression of nuclear AT1 receptors and angiotensin II within the kidney of the male congenic mRen2.Lewis rat Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1497 - F1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gonzalez-Villalobos, R. B. Klassen, P. L. Allen, K. Johanson, C. B. Baker, H. Kobori, L. G. Navar, and T. G. Hammond Megalin binds and internalizes angiotensin-(1-7) Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1270 - F1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Danilczyk and J. M. Penninger Angiotensin-Converting Enzyme II in the Heart and the Kidney Circ. Res., March 3, 2006; 98(4): 463 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. F. Benter, M. H. M. Yousif, J. T. Anim, C. Cojocel, and D. I. Diz Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H684 - H691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ferrario, A. J. Trask, and J. A. Jessup Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2281 - H2290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Riviere, A. Michaud, C. Breton, G. VanCamp, C. Laborie, M. Enache, J. Lesage, S. Deloof, P. Corvol, and D. Vieau Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat Hypertension, November 1, 2005; 46(5): 1169 - 1174. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
