ACE and ACE2 activity in diabetic mice

Jan Wysocki, Minghao Ye, Maria José Soler, Susan Gurley, Hong D. Xiao, Kenneth E. Bernstein, Thomas M. Coffman, Sheldon Chen, Daniel Batlle

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

ACE-related carboxypeptidase (ACE2) may counterbalance the angiotensin (ANG) II-promoting effects of ACE in tissues where both enzymes are found. Alterations in renal ACE and ACE2 expression have been described in experimental models of diabetes, but ACE2 activity was not assessed in previous studies. We developed a microplate-based fluorometric method for the concurrent determination of ACE and ACE2 activity in tissue samples. Enzymatic activity (relative fluorescence unit [RFU]·μg protein -1·h-1) was examined in ACE and ACE2 knockout mice and in two rodent models of diabetes, the db/db and streptozotocin (STZ)-induced diabetic mice. In kidney cortex, preparations consisting mainly of proximal tubules and cortical collecting tubules, ACE2 activity had a strong positive correlation with ACE2 protein expression (90-kDa band) in both knockout models and their respective wild-type littermates (r = 0.94, P < 0.01). ACE activity, likewise, had a strong positive correlation with renal cortex ACE protein expression (170-kDa band) (r = 0.838, P < 0.005). In renal cortex, ACE2 activity was increased in both models of diabetes (46.7 ± 4.4 vs. 22.0 ± 4.7 in db/db and db/m, respectively, P < 0.01, and 22.1 ± 2.8 vs. 13.1 ± 1.5 in STZ-induced diabetic versus untreated mice, respectively, P < 0.05). ACE2 mRNA levels in renal cortex from db/db and STZ-induced diabetic mice, by contrast, were not significantly different from their respective controls. In cardiac tissue, ACE2 activity was lower than in renal cortex, and there were no significant differences between diabetic and control mice (db/db 2.03 ± 0.23 vs. db/m 1.85 ± 0.10; STZ-induced diabetic 0.42 ± 0.04 vs. untreated 0.52 ± 0.07 mice). ACE2 activity in renal cortex correlated positively with ACE2 protein in db/db and db/m mice (r = 0.666, P < 0.005) as well as in STZ-induced diabetic and control mice (r = 0.621, P < 0.05) but not with ACE2 mRNA (r = -0.468 and r = -0.522, respectively). We conclude that in renal cortex from diabetic mice, ACE2 expression is increased at the posttranscriptional level. The availability of an assay for concurrent measurement of ACE and ACE2 activity should be helpful in the evaluation of kidney-specific alterations in the balance of these two carboxypeptidases, which are involved in the control of local ANG II formation and degradation.

Original languageEnglish (US)
Pages (from-to)2132-2139
Number of pages8
JournalDiabetes
Volume55
Issue number7
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Kidney
Streptozocin
Angiotensin II
Proteins
Carboxypeptidases
Kidney Cortex
Messenger RNA
Knockout Mice
Rodentia
Theoretical Models
Fluorescence
Enzymes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Wysocki, J., Ye, M., Soler, M. J., Gurley, S., Xiao, H. D., Bernstein, K. E., ... Batlle, D. (2006). ACE and ACE2 activity in diabetic mice. Diabetes, 55(7), 2132-2139. https://doi.org/10.2337/db06-0033

ACE and ACE2 activity in diabetic mice. / Wysocki, Jan; Ye, Minghao; Soler, Maria José; Gurley, Susan; Xiao, Hong D.; Bernstein, Kenneth E.; Coffman, Thomas M.; Chen, Sheldon; Batlle, Daniel.

In: Diabetes, Vol. 55, No. 7, 01.07.2006, p. 2132-2139.

Research output: Contribution to journalArticle

Wysocki, J, Ye, M, Soler, MJ, Gurley, S, Xiao, HD, Bernstein, KE, Coffman, TM, Chen, S & Batlle, D 2006, 'ACE and ACE2 activity in diabetic mice', Diabetes, vol. 55, no. 7, pp. 2132-2139. https://doi.org/10.2337/db06-0033
Wysocki J, Ye M, Soler MJ, Gurley S, Xiao HD, Bernstein KE et al. ACE and ACE2 activity in diabetic mice. Diabetes. 2006 Jul 1;55(7):2132-2139. https://doi.org/10.2337/db06-0033
Wysocki, Jan ; Ye, Minghao ; Soler, Maria José ; Gurley, Susan ; Xiao, Hong D. ; Bernstein, Kenneth E. ; Coffman, Thomas M. ; Chen, Sheldon ; Batlle, Daniel. / ACE and ACE2 activity in diabetic mice. In: Diabetes. 2006 ; Vol. 55, No. 7. pp. 2132-2139.
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abstract = "ACE-related carboxypeptidase (ACE2) may counterbalance the angiotensin (ANG) II-promoting effects of ACE in tissues where both enzymes are found. Alterations in renal ACE and ACE2 expression have been described in experimental models of diabetes, but ACE2 activity was not assessed in previous studies. We developed a microplate-based fluorometric method for the concurrent determination of ACE and ACE2 activity in tissue samples. Enzymatic activity (relative fluorescence unit [RFU]·μg protein -1·h-1) was examined in ACE and ACE2 knockout mice and in two rodent models of diabetes, the db/db and streptozotocin (STZ)-induced diabetic mice. In kidney cortex, preparations consisting mainly of proximal tubules and cortical collecting tubules, ACE2 activity had a strong positive correlation with ACE2 protein expression (90-kDa band) in both knockout models and their respective wild-type littermates (r = 0.94, P < 0.01). ACE activity, likewise, had a strong positive correlation with renal cortex ACE protein expression (170-kDa band) (r = 0.838, P < 0.005). In renal cortex, ACE2 activity was increased in both models of diabetes (46.7 ± 4.4 vs. 22.0 ± 4.7 in db/db and db/m, respectively, P < 0.01, and 22.1 ± 2.8 vs. 13.1 ± 1.5 in STZ-induced diabetic versus untreated mice, respectively, P < 0.05). ACE2 mRNA levels in renal cortex from db/db and STZ-induced diabetic mice, by contrast, were not significantly different from their respective controls. In cardiac tissue, ACE2 activity was lower than in renal cortex, and there were no significant differences between diabetic and control mice (db/db 2.03 ± 0.23 vs. db/m 1.85 ± 0.10; STZ-induced diabetic 0.42 ± 0.04 vs. untreated 0.52 ± 0.07 mice). ACE2 activity in renal cortex correlated positively with ACE2 protein in db/db and db/m mice (r = 0.666, P < 0.005) as well as in STZ-induced diabetic and control mice (r = 0.621, P < 0.05) but not with ACE2 mRNA (r = -0.468 and r = -0.522, respectively). We conclude that in renal cortex from diabetic mice, ACE2 expression is increased at the posttranscriptional level. The availability of an assay for concurrent measurement of ACE and ACE2 activity should be helpful in the evaluation of kidney-specific alterations in the balance of these two carboxypeptidases, which are involved in the control of local ANG II formation and degradation.",
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