Journal article
Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated fatty acids
The Biochemical journal, Vol.441(1), pp.359-366
01/01/2012
DOI: 10.1042/BJ20110626
PMCID: PMC3840540
PMID: 21880016
Abstract
Diets replete with n-3 poly-unsaturated fatty acids (n-3 PUFAs) are known to have therapeutic potential for the heart, although a specifically defined duration of n-3 PUFA diet required to achieve these effects remains unknown, as does their mechanism of action. This study was undertaken to establish whether adaptations in mitochondrial function and stress tolerance in the heart is evident following a short- (3 weeks) and long-term (14 weeks) dietary intervention of n-3 PUFAs, and to identify novel mechanisms by which these adaptations occur. Mitochondrial respiration (mO
2
), H
2
O
2
emission (mH
2
O
2
) and Ca
2+
retention capacity (mCa
2+
) were assessed in mouse hearts following dietary intervention. Mice fed n-3 PUFA’s for 14 weeks showed significantly lower mH
2
O
2
and greater mCa
2+
compared to all other groups. However, no significant differences were observed after 3 weeks of n-3 PUFA diet, or in mice fed a high fat diet devoid of n-3 PUFAs for 14 weeks. Interestingly, at 14 weeks n-3 PUFA mice had significantly greater glutathione reductase activity, reflected by a substantially higher GSH/GSSG ratio. Levels of protein adducts of 4-hydroxyhexenal, an aldehyde formed from peroxidation of n-3 PUFAs, were significantly elevated in n-3 PUFA fed mice, even at 3 weeks. These findings demonstrate distinct time-dependent effects of n-3 PUFAs on mitochondrial function and stress tolerance in the heart. In addition, they are first to provide direct evidence that increases in non-enzymatic lipid oxidation products precede these mitochondrial and redox-mediated adaptations, thereby revealing a novel mechanism for n-3 PUFA action in heart.
Details
- Title: Subtitle
- Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated fatty acids
- Creators
- Ethan J Anderson - Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC 27834Kathleen Thayne - Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC 27834Mitchel Harris - Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC 27834Kristen Carraway - Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC 27834Saame Raza Shaikh - Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC 27834
- Resource Type
- Journal article
- Publication Details
- The Biochemical journal, Vol.441(1), pp.359-366
- DOI
- 10.1042/BJ20110626
- PMID
- 21880016
- PMCID
- PMC3840540
- NLM abbreviation
- Biochem J
- ISSN
- 0264-6021
- eISSN
- 1470-8728
- Grant note
- R21 HL098780 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 01/01/2012
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984065690202771
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