Journal article
Recruitment of NADH shuttling in pressure-overloaded and hypertrophic rat hearts
American Journal of Physiology: Cell Physiology, Vol.292(5), pp.C1880-C1886
05/2007
DOI: 10.1152/ajpcell.00576.2006
PMCID: PMC1868664
PMID: 17229809
Abstract
Glucose metabolism in the heart requires oxidation of cytosolic NADH from glycolysis. This study examines shuttling reducing equivalents from the cytosol to the mitochondria via the activity and expression of the oxoglutarate-malate carrier (OMC) in rat hearts subjected to 2 wk (Hyp2, n = 6) and 10 wk (Hyp10, n = 8) of pressure overload hypertrophy vs. that of sham-operated rats (Sham2, n = 6; and Sham10, n = 7). Moderate aortic banding produced increased atrial natriuretic factor (ANF) mRNA expression at 2 and 10 wk, but only at 10 wk did hearts develop compensatory hypertrophy (33% increase, P < 0.05). Isolated hearts were perfused with the short-chain fatty acid [2,4-13C2]butyrate (2 mM) and glucose (5 mM) to enable dynamic-mode 13C NMR of intermediate exchange across OMC. OMC flux increased before the development of hypertrophy: Hyp2 = 9.6 ± 2.1 vs. Sham2 = 3.7 ± 1.2 μM·min−1·g dry wt−1, providing an increased contribution of cytosolic NADH to energy synthesis in the mitochondria. With compensatory hypertrophy, OMC flux returned to normal: Hyp10 = 3.9 ± 1.7 vs. Sham10 = 3.8 ± 1.2 μM·g−1·min−1. Despite changes in activity, no differences in OMC expression occurred between Hyp and Sham groups. Elevated OMC flux represented augmented cytosolic NADH shuttling, coupled to increased nonoxidative glycolysis, in response to hypertrophic stimulus. However, development of compensatory hypertrophy moderated the pressure-induced elevation in OMC flux, which returned to control levels. The findings indicate that the challenge of pressure overload increases cytosolic redox state and its contribution to mitochondrial oxidation but that hypertrophy, before decompensation, alleviates this stress response.
Details
- Title: Subtitle
- Recruitment of NADH shuttling in pressure-overloaded and hypertrophic rat hearts
- Creators
- E. Douglas LewandowskiJ. Michael O'DonnellThomas D ScholzNatalia SorokinaPeter M Buttrick
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.292(5), pp.C1880-C1886
- DOI
- 10.1152/ajpcell.00576.2006
- PMID
- 17229809
- PMCID
- PMC1868664
- NLM abbreviation
- Am J Physiol Cell Physiol
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 05/2007
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health
- Record Identifier
- 9984093505302771
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