Hypoxia in vivo decreases peroxisome proliferator-activated receptor alpha-regulated gene expression in rat heart.
We tested the hypothesis that hypoxia decreases PPARalpha-regulated gene expression in heart muscle in vivo. In two rat models of systemic hypoxia (cobalt chloride treatment and iso-volemic hemodilution), transcript levels of PPARalpha and PPARalpha-regulated genes (pyruvate dehydrogenase kinase 4 (PDK4), muscle carnitine palmitoyltransferase-I (mCPT-I), and malonyl-CoA decarboxylase (MCD)) were measured using real-time quantitative RT-PCR. Data were normalized to the housekeeping gene beta-actin. Atrial natriuretic factor (ANF) and pyruvate dehydrogenase kinase 2 (PDK2), which are not regulated by PPARalpha, served as controls. CoCl(2) treatment decreased PPARalpha, PDK4, mCPT-I, and MCD mRNA levels. Iso-volemic anemia also caused a significant decrease in PPARalpha, PDK4, and MCD mRNA levels. Transcript levels of mCPT-I showed a slight, but not significant decrease (P = 0.08). Gene expression of beta-actin, ANF, and PDK2 did not change with either CoCl(2) treatment nor with anemia. Myocardial PPARalpha-regulated gene expression is decreased in two models of hypoxia in vivo. These results suggest a transcriptional mechanism for decreased fatty oxidation and increased reliance of the heart for glucose during hypoxia.
Razeghi
P
P
Division of Cardiology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Young
M E
ME
Abbasi
S
S
Taegtmeyer
H
H
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology*; D015536:Down-Regulation; D004734:Energy Metabolism; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006438:Hemodilution; D000860:Hypoxia; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D007527:Isoenzymes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003035:Cobalt; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; C018021:cobaltous chloride; D010100:Oxygen