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Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles.
- Source :
-
The Journal of physiology [J Physiol] 2003 Sep 01; Vol. 551 (Pt 2), pp. 491-501. Date of Electronic Publication: 2003 Jun 24. - Publication Year :
- 2003
-
Abstract
- Congestive heart failure (CHF) induces alterations in energy metabolism and mitochondrial function that span cardiac as well as skeletal muscles. Whether these defects originate from altered mitochondrial DNA copy number and/or mitochondrial gene transcription is not known at present, nor are the factors that control mitochondrial capacity in different muscle types completely understood. We used an experimental model of CHF induced by aortic banding in the rat and investigated mitochondrial respiration and enzyme activity of biochemical mitochondrial markers in cardiac, slow and fast skeletal muscles. We quantified mitochondrial DNA (mtDNA), expression of nuclear (COX IV) and mitochondrial (COX I) encoded cytochrome c oxidase subunits as well as nuclear factors involved in mitochondrial biogenesis and in the necessary coordinated interplay between nuclear and mitochondrial genomes in health and CHF. CHF induced a decrease in oxidative capacity and mitochondrial enzyme activities with a parallel decrease in the mRNA level of COX I and IV, but no change in mtDNA content. The expression of the peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC-1 alpha) gene was downregulated in CHF, as well as nuclear respiratory factor 2 and mitochondrial transcription factor A, which act downstream from PGC-1 alpha. Most interestingly, only the level of PGC-1 alpha expression was strongly correlated with muscle oxidative capacity in cardiac and skeletal muscles, both in healthy and CHF rats. Mitochondrial gene transcription is reduced in CHF, and PGC-1 alpha appears as a potential modulator of muscle oxidative capacity under these experimental conditions.
- Subjects :
- Animals
Blotting, Southern
Body Weight physiology
Citrate (si)-Synthase biosynthesis
Citrate (si)-Synthase genetics
DNA Primers
DNA, Mitochondrial biosynthesis
Gene Expression Regulation, Enzymologic genetics
Gene Expression Regulation, Enzymologic physiology
Heart Failure enzymology
Kinetics
Mitochondria, Heart enzymology
Mitochondria, Muscle enzymology
Muscle, Skeletal enzymology
Myocardium enzymology
Myocardium metabolism
Organ Size physiology
Oxidation-Reduction
Oxidative Phosphorylation
Prostaglandin-Endoperoxide Synthases biosynthesis
Prostaglandin-Endoperoxide Synthases genetics
RNA, Messenger biosynthesis
Rats
Reverse Transcriptase Polymerase Chain Reaction
Heart physiology
Heart Failure metabolism
Mitochondria, Heart metabolism
Mitochondria, Muscle metabolism
Muscle, Skeletal metabolism
Transcription Factors biosynthesis
Transcription, Genetic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3751
- Volume :
- 551
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- The Journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12824444
- Full Text :
- https://doi.org/10.1113/jphysiol.2003.045104