Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats

Show simple item record Jullig, Maria en Hickey, Anthony en Chai, CC en Skea, Gretchen en Middleditch, MJ en Costa, S en Choong, SY en Philips, ARJ en Cooper, Garth en 2012-03-16T02:31:48Z en 2008-06 en
dc.identifier.citation Proteomics 8(12):2556-2572 Jun 2008 en
dc.identifier.issn 1615-9853 en
dc.identifier.uri en
dc.description.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 (TM)-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. en
dc.language EN en
dc.publisher WILEY-VCH Verlag GmbH & Co en
dc.relation.ispartofseries Proteomics en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.subject cardiac failure en
dc.subject hypertension en
dc.subject metabolic pathways en
dc.subject mitochondrion en
dc.subject protein mass spectrometry en
dc.subject FATTY-ACID en
dc.subject CARDIAC-FAILURE en
dc.subject LEFT-VENTRICLE en
dc.subject ALTERED GLUCOSE en
dc.subject SKELETAL-MUSCLE en
dc.subject KETONE-BODIES en
dc.title Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats en
dc.type Journal Article en
dc.identifier.doi 10.1002/pmic.200700977 en
pubs.issue 12 en
pubs.begin-page 2556 en
pubs.volume 8 en
dc.rights.holder Copyright: WILEY-VCH Verlag GmbH & Co en
dc.identifier.pmid 18563753 en
pubs.end-page 2572 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 80245 en Science en Biological Sciences en Science Research en Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 18563753 en

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