Angiotensin-Converting Enzyme 2 (ACE2) Human ELISA

Summary

By EST database searching for sequences showing homology to the zinc metalloprotease angiotensin-I converting enzyme, a full-length ACE2 cDNA, originally called ACEH, was isolated, which encoded a deduced 805-amino acid protein that shares approximately 40% identity with the N- and C-terminal domains of ACE. ACE2 contains a potential 17-amino acid N-terminal signal peptide and a putative 22-amino acid C-terminal membrane anchor. Northern blot analysis detected high expression of ACE2 in kidney, testis, and heart, and moderate expression in colon, small intestine, and ovary. Tipnis et al. expressed a soluble, truncated form of ACE2 lacking transmembrane and cytosolic domains in CHO cells and found that it produced a glycosylated protein that was able to cleave angiotensin I and angiotensin II , but not bradykinin. Boehm and Nabel showed whereas ACE converts angiotensin I to angiotensin II, which has 8 amino acids, ACE2 converts angiotensin I to angiotensin 1–9, which has 9 amino acids. This can then further be converted by ACE to a shorter peptide, angiotensin 1–7, which is a blood vessel dilator. Using ACE2 null mice, Crackower et al. showed that ACE2 was critically involved in a cardiac contractility. Li et al. identified ACE2, isolated from SARS coronavirus-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS coronavirus S protein. It was shown that when ACE2 was engaged with S protein ACE2 surface expression was downregulated, increasing lung levels of angiotensin II, which was proposed to give rise to a severe lung injury. Since ACE2 is detected in urine, measurement of shedded ACE2 may provide a novel clue to renal & cardiovascular function of ACE2.

Research topic

Blood pressure regulation and NO metabolism, Renal disease

Assay format

Sandwich ELISA, Biotin-labelled antibody

Applications

Cell culture supernatant, Urine

Storage/Shipping

+4°C. After standard reconstitution, prepare aliquots and store at –20°C. Avoid freeze/thaw cycles. Plate and reagents should reach room temperature before use.

Calibration Curve

Calibration range

0.39 to 25 ng/ml

Limit of detection

293 pg/ml

References to this product

• Kira JI, Miki T, Horiuchi M, Kohara K, Tsukuda K, Ohyagi Y, Matsuoka T, Higaki N, Mogi M, Kawajiri M. Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis. Mult Scler. 2009 Feb;15 (2):262-5

References to summary

• Boehm M, Nabel EG. Angiotensin-converting enzyme 2--a new cardiac regulator. N Engl J Med. 2002 Nov 28;347 (22):1795-7
• Farzan M, Choe H, Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426 (6965):450-4
• Penninger JM, Jiang C, Slutsky AS, Uhlig S, Hein L, Hui CC, Fukamizu A, Crackower MA, Leong-Poi H, Wada T, Sarao R, Yang P, Guan B, Guo F, Huan Y, Rao S, Kuba K, Imai Y. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005 Jul 7;436 (7047):112-6
• Penninger JM, Yagil Y, Chappell MC, Manoukian AS, Ferrario CM, Scholey J, Pei Y, Zhang L, da Costa J, Oliveira-dos-Santos AJ, Scanga SE, Kozieradzki I, Yagil C, Oudit GY, Sarao R, Crackower MA, Backx PH. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002 Jun 20;417 (6891):822-8
• Turner AJ, Christie G, Karran E, Hyde R, Hooper NM, Tipnis SR. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275 (43):33238-43

By research topic:

• Blood pressure regulation and NO metabolism
• Renal disease

By molecule:

• Angiotensin-Converting Enzyme 2