Characterization of ACE and ACE2 Expression Within Different Organs of the NOD Mouse

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Mar 10

PMID 28273875

Citations 161

Authors

Heleia Roca-Ho

Marta Riera

Vanesa Palau

Julio Pascual

Maria Jose Soler

Affiliations

Soon will be listed here.

Abstract

Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

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References

Huang W, Gallois Y, Bouby N, Bruneval P, Heudes D, Belair M . Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci U S A. 2001; 98(23):13330-4. PMC: 60870. DOI: 10.1073/pnas.231476798. View

Ye M, Wysocki J, William J, Soler M, Cokic I, Batlle D . Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes. J Am Soc Nephrol. 2006; 17(11):3067-75. DOI: 10.1681/ASN.2006050423. View

Paul M, Poyan Mehr A, Kreutz R . Physiology of local renin-angiotensin systems. Physiol Rev. 2006; 86(3):747-803. DOI: 10.1152/physrev.00036.2005. View

Oliveira E, Santos R, Krieger J . Standardization of a fluorimetric assay for the determination of tissue angiotensin-converting enzyme activity in rats. Braz J Med Biol Res. 2000; 33(7):755-64. DOI: 10.1590/s0100-879x2000000700005. View

Xiao X, Ma B, Dong B, Zhao P, Tai N, Chen L . Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. J Autoimmun. 2009; 32(2):85-93. DOI: 10.1016/j.jaut.2008.12.003. View

Soler M, Wysocki J, Batlle D . Angiotensin-converting enzyme 2 and the kidney. Exp Physiol. 2008; 93(5):549-56. DOI: 10.1113/expphysiol.2007.041350. View

Anguiano L, Riera M, Pascual J, Valdivielso J, Barrios C, Betriu A . Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease. Atherosclerosis. 2016; 253:135-143. DOI: 10.1016/j.atherosclerosis.2016.08.032. View

Harmer D, Gilbert M, Borman R, Clark K . Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532(1-2):107-10. DOI: 10.1016/s0014-5793(02)03640-2. View

Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H . Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2):631-7. PMC: 7167720. DOI: 10.1002/path.1570. View

10.

Anguiano L, Riera M, Pascual J, Valdivielso J, Barrios C, Betriu A . Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease. Nephrol Dial Transplant. 2015; 30(7):1176-85. PMC: 7107869. DOI: 10.1093/ndt/gfv025. View

11.

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B . Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436(7047):112-6. PMC: 7094998. DOI: 10.1038/nature03712. View

12.

Marquez E, Riera M, Pascual J, Soler M . Albumin inhibits the insulin-mediated ACE2 increase in cultured podocytes. Am J Physiol Renal Physiol. 2014; 306(11):F1327-34. DOI: 10.1152/ajprenal.00594.2013. View

13.

Gembardt F, Sterner-Kock A, Imboden H, Spalteholz M, Reibitz F, Schultheiss H . Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents. Peptides. 2005; 26(7):1270-7. PMC: 7115528. DOI: 10.1016/j.peptides.2005.01.009. View

14.

Riordan J . Angiotensin-I-converting enzyme and its relatives. Genome Biol. 2003; 4(8):225. PMC: 193637. DOI: 10.1186/gb-2003-4-8-225. View

15.

Kasahara Y, ASHIHARA Y . Colorimetry of angiotensin-I converting enzyme activity in serum. Clin Chem. 1981; 27(11):1922-5. View

16.

Ortiz-Perez J, Riera M, Bosch X, de Caralt T, Perea R, Pascual J . Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study. PLoS One. 2013; 8(4):e61695. PMC: 3632515. DOI: 10.1371/journal.pone.0061695. View

17.

Bindom S, Hans C, Xia H, Boulares A, Lazartigues E . Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice. Diabetes. 2010; 59(10):2540-8. PMC: 3279528. DOI: 10.2337/db09-0782. View

18.

Averill D, Ishiyama Y, Chappell M, Ferrario C . Cardiac angiotensin-(1-7) in ischemic cardiomyopathy. Circulation. 2003; 108(17):2141-6. DOI: 10.1161/01.CIR.0000092888.63239.54. View

19.

Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J . Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002; 277(17):14838-43. DOI: 10.1074/jbc.M200581200. View

20.

Schwager S, Carmona A, Sturrock E . A high-throughput fluorimetric assay for angiotensin I-converting enzyme. Nat Protoc. 2007; 1(4):1961-4. DOI: 10.1038/nprot.2006.305. View