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

Autor: Yoshio Kodera, Tsuneo Takenaka, Pamela K. Carmines, Yoshikazu Aoki, Masanori Yokoba, Tadakazu Maeda, Naohito Ishii, Masato Katagiri, Masamichi Oh-Ishi, Tsuyoshi Ichikawa, Hiroyuki Imaizumi, Hideki Ikenagasa
Rok vydání: 2013
Předmět:
BP
blood pressure
Male
Angiotensin-Converting Enzyme Inhibitors
STZ+ENAL
enalapril-treated STZ rats
urologic and male genital diseases
ACEi
angiotensin-converting enzyme inhibitor(s)
Rats
Sprague-Dawley
chemistry.chemical_compound
DM
diabetes mellitus
MS/MS
tandem MS
3-NT
3-nitrotyrosine
oxidative stress
MMSDH
methylmalonate-semialdehyde dehydrogenase
biology
LC
liquid chromatography
2-DE
two-dimensional gel electrophoresis
Chemistry
Superoxide
ACO2
General Medicine
proteomic analysis
NOx
nitrate+nitrite
medicine.anatomical_structure
Glutamate dehydrogenase 1
NNA
Nω-nitro-L-arginine
Sham+ENAL
enalapril-treated Sham rats
medicine.drug
GDH1
glutamate dehydrogenase 1
medicine.medical_specialty
Kidney Cortex
Renal cortex
TCA
tricarboxylic acid
S6
Peptidyl-Dipeptidase A
STZ
streptozotocin
S4
ACO2
aconitase 2
Mitochondrial Proteins
Superoxide dismutase
DN
diabetic nephropathy
nitric oxide
SOD
superoxide dismutase
Internal medicine
medicine
Animals
Humans
Enalapril
3-nitrotyrosine
Original Paper
NO
nitric oxide
NBT
Nitro Blue Tetrazolium
diabetic nephropathy
GFR
glomerular filtration rate
HBSS
Hank’s balanced salt solution
Angiotensin-converting enzyme
Streptozotocin
O2−
superoxide anion
ONOO−
peroxynitrite
Rats
Disease Models
Animal
Diabetes Mellitus
Type 1
Endocrinology
biology.protein
PEPCK
phosphoenolpyruvate carboxykinase
Tyrosine
Zdroj: Clinical Science (London, England : 1979)
ISSN: 1470-8736
0143-5221
Popis: 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. O2− (superoxide anion) and NOx (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 O2− and 3-NT was increased in DM rats; however, enalapril suppressed these changes. DM rats also exhibited elevated renal cortical NOx 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.
Databáze: OpenAIRE
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