Juellig 2008 Proteomics
| 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. |
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
