Juellig 2008 Proteomics

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Jüllig M, Hickey AJ, Chai CC, Skea GL, Middleditch MJ, Costa S, Choong SY, Philips AR, Cooper GJ (2008) Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats. Proteomics 8:2556-72.

» PMID: 18563753

Juellig M, Hickey AJ, Chai CC, Skea GL, Middleditch MJ, Costa S, Choong SY, Philips AR, Cooper GJ (2008) Proteomics

Abstract: Hypertension now affects about 600 million people worldwide and is a leading cause of death in the Western world. The spontaneously hypertensive rat (SHR), provides a useful model to investigate hypertensive heart failure (HF). The SHR model replicates the clinical progression of hypertension in humans, wherein early development of hypertension is followed by a long stable period of compensated cardiac hypertrophy that slowly progresses to HF. Although the hypertensive failing heart generally shows increased substrate preference towards glucose and impaired mitochondrial function, the cause-and-effect relationship between these characteristics is incompletely understood. To explore these pathogenic processes, we compared cardiac mitochondrial proteomes of 20-month-old SHR and Wistar-Kyoto controls by iTRAQ™-labelling combined with multidimensional LC/MS/MS. Of 137 high-scoring proteins identified, 79 differed between groups. Changes were apparent in several metabolic pathways, chaperone and antioxidant systems, and multiple subunits of the oxidative phosphorylation complexes were increased (complexes I, III and IV) or decreased (complexes II and V) in SHR heart mitochondria. Respiration assays on skinned fibres and isolated mitochondria showed markedly lower respiratory capacity on succinate. Enzyme activity assays often also showed mismatches between increased protein expression and activities suggesting elevated protein expression may be compensatory in the face of pathological stress.

Keywords: Cardiac failure, Hypertension, Metabolic pathways, Mitochondrion, Protein mass spectrometry

O2k-Network Lab: NZ Auckland Hickey AJ


Labels:

Stress:Mitochondrial disease  Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue, Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: OXPHOS 

HRR: Oxygraph-2k