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

Content Provider	Springer Nature Link
Author	Zungu, Makhosazane Young, Martin E. Stanley, William C. Essop, M. Faadiel
Copyright Year	2009
Abstract	We 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.
Starting Page	55
Ending Page	62
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	330
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2009-04-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Wy-14,643 Uncoupling Mitochondrial respiration Cardiac contractile function UCP3 Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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