Published online before print March 14, 2002, doi: 10.1161/01.RES.0000015592.95986.03
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Submitted on November 5, 2001
Revised on March 6, 2002
Accepted on March 6, 2002
Hypoxia Causes Downregulation of Protein and RNA Synthesis in Noncontracting Mammalian Cardiomyocytes
Tammy M. Casey *;
From the Department of Biochemistry, The University of Western Australia, Crawley, Australia, and the Western Australian Institute for Medical Research, Perth, Australia.
* To whom correspondence should be addressed. E-mail: tmcasey{at}cyllene.uwa.edu.au.
The aim was to identify energy-consuming processes, other than contraction, downregulated during moderate hypoxia (
5 µmol/L, 0.5% O2) and severe hypoxia (<0.5 µmol/L, <0.05% O2) in isolated neonatal cardiomyocytes. The metabolic response of cardiomyocytes to moderate and severe hypoxia was assessed by measuring rates of energy consumption and energetic status of cells maintained under these conditions. We found that the rates of energy production were decreased during both forms of hypoxia. Decreased rates of energy production under moderate hypoxia were associated with reduced energy wastage through a downregulation of proton leak in the mitochondria. Cellular protein synthesis and RNA synthesis, major energy-consuming pathways, were downregulated only during severe hypoxia, when oxygen concentrations were low enough to induce energetic stress (quantitatively defined as being any situation in which phosphocreatine concentrations had fallen by 
40%). Our results suggest that energetic stress is the signal responsible for this downregulation.
Key words: cardiomyocytes • hypoxia • protein synthesis • RNA synthesis • Na+,K+-ATPase activity • proton leak
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