Quantitative Proteome
of Medulla Oblongata in Spontaneously
Hypertensive Rats
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Abstract
We performed an extensive quantitative proteomic analysis
on the
pooled medulla sample of the 11-week-old spontaneously hypertensive
rats (SHR) compared to age-matched normotensive Wistar rats, using
iTRAQ technology coupled with nano two-dimentional liquid chromatography
followed by high resolution mass spectrometric abundance indexes techniques.
Many differentially expressed proteins identified were involved in
energy metabolism, such as mitochondrial part, pyruvate dehydrogenase
complex, and respiratory chain. These proteins were included in citrate
cycle (TCA cycle), pyruvate metabolism and oxidative phosphorylation.
The proteomic analysis and subsequent Western blotting on two independent
cohorts of animials indicated that the dysregulation of energy metabolism
existed in the medulla of the SHR rats. The differentially expressed
proteins in the dysregulation of energy metabolism in the medulla
of SHR rats included down-regulated ATP6V1D, ATP6VOA1, ATP5L, DLD
proteins and up-regulated AK1 protein. MAO-A protein also exhibited
decreased regulation, as well as the other 3 above-mentioned energy-relative
proteins (ATP6V1D, ATP5L and DLD proteins) belonging to the heterocycle
metabolic process. A receiver operating characteristic curve (ROC)
analysis on 4 of the differentially expressed proteins respectively
resulted in an area under the receiver operating characteristic curve
(AUC) of 0.95, 0.90, 0.92, and 0.81 for differentiating the SHR rats
from the normotensive rats. This dysfunction in energy metabolism
localizes to the medulla, the lower part of brain stem, and is, therefore,
likely to contribute to the development, as well as to pathophysiological
complications of hypertension