Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse.

Heleia Roca-Ho,Maria Soler,Julio Pascual,Vanesa Palau,Marta Riera

doi:10.3390/ijms18030563

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.

Highlights

Angiotensin converting enzyme (ACE)2 is an enzymatically active ACE homologue, which shares 42% of its amino acidic sequence identity in its catalytic domain; ACE and ACE2 show several differences
We observed that ACE activity at lower human recombinant ACE (hrACE) amounts was only detected by the use of Borate Buffer (BB)
The hrACE activity measurement was found to be linear with BB as compared to Phosphate Buffer (PB)

Summary

Introduction

Angiotensin converting enzyme (ACE) is an enzymatically active ACE homologue, which shares 42% of its amino acidic sequence identity in its catalytic domain; ACE and ACE2 show several differences. Whereas ACE is a dipeptidylcarboxypeptidase, presenting both N- and C-terminus catalytic domains with two zinc-binding motifs (HEXXH, where X is any amino acid); ACE2 is a monocarboxypeptidase with only one zinc-binding motif at its N-terminal domain [1,2,3]. Through this catalytic domain, ACE2 hydrolyzes AngII (angiotensin II) to generate Ang, a peptide that binds to the MAS receptor (Ang receptor) and activates vasodilation, anti-fibrosis, anti-proliferation, and anti-inflammatory effects as well as counterbalances the ACE-AngII-ATR1 axis actions [4,5,6]. ACE expression was mainly found in the surface of endothelial cells of lungs, renal brush border membranes, intestines, choroid plexus, placenta [9,10,11], and, to a lesser extent, in cardiac, hepatic, pancreatic, and adrenal tissues [12]

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