Chronic treatment with the peroxisome proliferator-activated receptor α agonist Wy-14,643 attenuates myocardial respiratory capacity and contractile function

Simple item page
dc.contributor.authorZungu M.
dc.contributor.authorYoung M.E.
dc.contributor.authorStanley W.C.
dc.contributor.authorEssop M.F.
dc.date.accessioned2011-05-15T16:00:00Z
dc.date.available2011-05-15T16:00:00Z
dc.date.issued2009
dc.description.abstractWe investigated whether chronic in vivo treatment with the peroxisome proliferator-activated receptor α agonist Wy-14,643 attenuates cardiac contractile function by impairing mitochondrial respiration. Wy-14,643 (25 mg kg-1 day-1) was administered to Wistar rats by oral gavage for 14 consecutive days, after which ex vivo heart function, myocardial mitochondrial respiratory capacity, and metabolic gene expression were determined. Body and heart weights were not significantly altered following 14 days of Wy-14,643 administration. Heart perfusion studies showed significantly reduced systolic and developed pressures, while the rate pressure product declined by 36 ± 2.6% (P < 0.01 vs. vehicle) after 14 days of Wy-14,643 treatment. State 3 mitochondrial respiration was lower in the Wy-14,643 group (P = 0.06 vs. vehicle). State 4 respiration and oligomycin-insensitive proton leak were significantly increased compared with matched controls. The rate of ADP phosphorylation was also decreased by 44.9 ± 1.9% (P < 0.05 vs. vehicle). Pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) transcript levels were upregulated, while cytochrome oxidase II (COXII) expression was decreased following Wy-14,643 treatment. This study demonstrates that chronic in vivo Wy-14,643 administration impaired cardiac contractile function in parallel with decreased mitochondrial respiratory function and increased uncoupling. © 2009 Springer Science+Business Media, LLC.
dc.description.versionArticle
dc.identifier.citationMolecular and Cellular Biochemistry
dc.identifier.citation330
dc.identifier.citation02-Jan
dc.identifier.issn3008177
dc.identifier.other10.1007/s11010-009-0100-y
dc.identifier.urihttp://hdl.handle.net/10019.1/11474
dc.subjectadenosine diphosphate
dc.subjectcytochrome c oxidase
dc.subjectcytochrome c oxidase 2
dc.subjectphosphotransferase
dc.subjectpirinixic acid
dc.subjectpyruvate dehydrogenase
dc.subjectpyruvate dehydrogenase kinase 4
dc.subjectunclassified drug
dc.subjectuncoupling protein 3
dc.subjectanimal cell
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectblood pressure measurement
dc.subjectbody weight
dc.subjectcontrolled study
dc.subjectgene expression
dc.subjectheart muscle contractility
dc.subjectheart perfusion
dc.subjectheart weight
dc.subjectmale
dc.subjectmitochondrial respiration
dc.subjectnonhuman
dc.subjectoxidative phosphorylation
dc.subjectrat
dc.subjectrespiratory function
dc.subjectsystolic blood pressure
dc.subjectupregulation
dc.subjectWistar rat
dc.subjectAnimals
dc.subjectAnticholesteremic Agents
dc.subjectCell Respiration
dc.subjectMale
dc.subjectMitochondria, Heart
dc.subjectMyocardial Contraction
dc.subjectPeroxisome Proliferators
dc.subjectPPAR alpha
dc.subjectPyrimidines
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectUncoupling Agents
dc.subjectRattus norvegicus
dc.titleChronic treatment with the peroxisome proliferator-activated receptor α agonist Wy-14,643 attenuates myocardial respiratory capacity and contractile function
dc.typeArticle
Files
Collections
Stellenbosch University - Scopus Publications