Wy-14,643 and fenofibrate inhibit mitochondrial respiration in isolated rat cardiac mitochondria.
We investigated the direct effects of two selective PPARalpha ligands, fenofibrate and Wy-14,643, on mitochondrial respiratory function using isolated rat cardiac mitochondria. Isolated left ventricular mitochondria were incubated with increasing concentrations of fenofibrate or Wy-14,643 (10, 100, and 500 microM) and mitochondrial respiration determined using: malate/glutamate (complex I), succinate (complex II) and palmitoyl-l-carnitine as oxidative substrates. Our data show that acute exposure to Wy-14,643 and fenofibrate differentially perturb cardiac mitochondrial respiration i.e., fenofibrate more potently inhibited mitochondrial respiration and bioenergetic capacity compared to Wy-14,643. Moreover, we found that both agents increased uncoupling of mitochondrial oxidative phosphorylation.
Zungu
Makhosazane
M
Hatter Heart Research Institute, Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
Felix
Rebecca
R
Essop
M Faadiel
MF
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011743:Pyrimidines; C006253:pirinixic acid; D011345:Fenofibrate