Hypoxia causes downregulation of protein and RNA synthesis in noncontracting Mammalian cardiomyocytes.

Abstract:

:The aim was to identify energy-consuming processes, other than contraction, downregulated during moderate hypoxia ( approximately 5 micromol/L, 0.5% O(2)) and severe hypoxia (<0.5 micromol/L, <0.05% O(2)) 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 > or = 40%). Our results suggest that energetic stress is the signal responsible for this downregulation.

journal_name

Circ Res

journal_title

Circulation research

authors

Casey TM,Pakay JL,Guppy M,Arthur PG

doi

10.1161/01.res.0000015592.95986.03

subject

Has Abstract

pub_date

2002-04-19 00:00:00

pages

777-83

issue

7

eissn

0009-7330

issn

1524-4571

journal_volume

90

pub_type

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