Hypoxia in Vivo Decreases Peroxisome Proliferator-Activated Receptor α-Regulated Gene Expression in Rat Heart

• Published in: Biochemical and biophysical research communications 2001-09, Vol.287 (1), p.5-10
• Main Authors: Razeghi, Peter, Young, Martin E., Abbasi, Shahrzad, Taegtmeyer, Heinrich
• Format: Article
• Language: English
• Subjects: Animals; Carboxy-Lyases - metabolism; Carnitine O-Palmitoyltransferase - metabolism; Cobalt - pharmacology; cobalt chloride; Down-Regulation; Energy Metabolism; Gene Expression - drug effects; Heart - drug effects; Heart - physiology; Hemodilution; Hypoxia; iso-volemic hemodilution; Isoenzymes - metabolism; Male; Myocardium - metabolism; Oxygen - metabolism; ppar; Protein Kinases - metabolism; pyruvate dehydrogenase kinase 2; pyruvate dehydrogenase kinase 4; quantitative RT-PCR; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Cytoplasmic and Nuclear - physiology; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.5541

We tested the hypothesis that hypoxia decreases PPARα-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 PPARα and PPARα-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 β-actin. Atrial natriuretic factor (ANF) and pyruvate dehydrogenase kinase 2 (PDK2), which are not regulated by PPARα, served as controls. CoCl2 treatment decreased PPARα, PDK4, mCPT-I, and MCD mRNA levels. Iso-volemic anemia also caused a significant decrease in PPARα, PDK4, and MCD mRNA levels. Transcript levels of mCPT-I showed a slight, but not significant decrease (P = 0.08). Gene expression of β-actin, ANF, and PDK2 did not change with either CoCl2 treatment nor with anemia. Myocardial PPARα-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.