Angiotensin-converting enzyme inhibition curbs tyrosine nitration of mitochondrial proteins in the renal cortex during the early stage of diabetes mellitus in rats.

Abstract

Experiments were performed to evaluate the hypothesis that ACE (angiotensin-converting enzyme) inhibition (enalapril) suppresses 3-NT (3-nitrotyrosine) production in the renal cortex during the early stage of Type 1 DM (diabetes mellitus) in the rat. Enalapril was administered chronically for 2 weeks to subsets of STZ (streptozotocin)-induced DM and vehicle-treated sham rats. O(2)(-) (superoxide anion) and NO(x) (nitrate+nitrite) levels were measured in the media bathing renal cortical slices after 90 min incubation in vitro. SOD (superoxide dismutase) activity and 3-NT content were measured in the renal cortex homogenate. Renal cortical nitrated protein was identified by proteomic analysis. Renal cortical production of O(2)(-) and 3-NT was increased in DM rats; however, enalapril suppressed these changes. DM rats also exhibited elevated renal cortical NO(x) production and SOD activity, and these changes were magnified by enalapril treatment. 2-DE (two-dimensional gel electrophoresis)-based Western blotting revealed more than 20 spots with positive 3-NT immunoreactivity in the renal cortex of DM rats. Enalapril treatment blunted the DM-induced increase in tyrosine nitration of three proteins ACO2, GDH1 and MMSDH (aconitase 2, glutamate dehydrogenase 1 and methylmalonate-semialdehyde dehydrogenase), each of which resides in mitochondria. These data are consistent with enalapril preventing DM-induced tyrosine nitration of mitochondrial proteins by a mechanism involving suppression of oxidant production and enhancement of antioxidant capacity, including SOD activation.

• Authors: Naohito Ishii, Pamela K Carmines, Masanori Yokoba, Hiroyuki Imaizumi, Tsuyoshi Ichikawa, Hideki Ikenagasa, Yoshio Kodera, Masamichi Oh-Ishi, Yoshikazu Aoki, Tadakazu Maeda, Tsuneo Takenaka, Masato Katagiri
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 124 Issue 8 Pg. 543-52 (Apr 2013) ISSN: 1470-8736 [Electronic] England
• PMID: 23130652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Mitochondrial Proteins
• 3-nitrotyrosine
• Tyrosine
• Peptidyl-Dipeptidase A

Topics

• Angiotensin-Converting Enzyme Inhibitors (administration & dosage)
• Animals
• Diabetes Mellitus, Type 1 (drug therapy, genetics, metabolism)
• Disease Models, Animal
• Humans
• Kidney Cortex (drug effects, enzymology, metabolism)
• Male
• Mitochondrial Proteins (metabolism)
• Peptidyl-Dipeptidase A (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tyrosine (analogs & derivatives, metabolism)