Cellular Redox Activity of Coenzyme Q 10 : Effect of CoQ 10 Supplementation on Human Skeletal Muscle

Abstract

In this paper, we report results obtained from a continuing clinical trial on the effect of coenzyme Q10 (CoQ10) administration on human vastus lateralis (quadriceps) skeletal muscle. Muscle samples, obtained from aged individuals receiving placebo or CoQ10 supplementation (300mg per day for four weeks prior to hip replacement surgery) were analysed for changes in gene and protein expression and in muscle fibre type composition. Microarray analysis (Affymetrix U95A human oligonucleotide array) using a change in gene expression of 1.8-fold or greater as a cutoff point, demonstrated that a total of 115 genes were differentially expressed in six subject comparisons. In the CoQ10-treated subjects, 47 genes were up-regulated and 68 down-regulated in comparison with placebo-treated subjects. Restriction fragment differential display analysis showed that over 600 fragments were differentially expressed using a 2.0-fold or greater change in expression as a cutoff point. Proteome analysis revealed that, of the high abundance muscle proteins detected (2,086 +/- 115), the expression of 174 proteins was induced by CoQ10 while 77 proteins were repressed by CoQ10 supplementation. Muscle fibre types were also affected by CoQ10 treatment; CoQ10-treated individuals showed a lower proportion of type I (slow twitch) fibres and a higher proportion of type IIb (fast twitch) fibres, compared to age-matched placebo-treated subjects. The data suggests that CoQ10 treatment can act to influence the fibre type composition towards the fibre type profile generally found in younger individuals. Our results led us to the conclusion that coenzyme Q10 is a gene regulator and consequently has wide-ranging effects on over-all tissue metabolism. We develop a comprehensive hypothesis that CoQ10 plays a major role in the determination of membrane potential of many, if not all, sub-cellular membrane systems and that H2O2 arising from the activities of CoQ10 acts as a second messenger for the modulation of gene expression and cellular metabolism.

A randomized, double-blind trial on the bioavailability of two CoQ10 formulations

“…Blood CoQ10 levels of 2.4 lg/ml were demonstrated as having the highest benefit in congestive heart failure, while levels of at least 3.4 lg/ml were needed before therapeutic effects were seen from dietary supplementation in patients with congestive heart failure (Linnane et al, 2002). However, in neurodegenerative disease conditions the required plasma threshold levels appear to be much higher to produce a clinical response.…”

Functional connections and pathways of coenzyme Q10‐inducible genes: An in‐silico study

“…The molecular mechanisms by which CoQ 10 mediates these beneficial effects are uncertain. We (25) and others (26,27) obtained evidence that CoQ 10 influences the expression of hundreds of genes involved in different cellular pathways. To decipher the functional and regulatory connections of these genes we employed bioinformatic techniques to access the actions of CoQ 10 in detail.…”

Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide

“…Age related decline in bioenergy capacity below a crucial threshold will obviously contribute to cellular malfunction. The development of mitochondrial tissue bioenergy mosaics with age, exemplified by null, low and normal cytochrome oxidase cell content has been stringently correlated at the single cell level by our laboratory, with mtDNA deletions and the individual cell content of full-length functional mtDNA (Nagley et al 1993;Kovalenko et al 1998;Kopsidas et al 2000Kopsidas et al , 2002Linnane et al 2002a). The mtDNA deletion changes reported by us mainly arise by replication error due to the asymmetrical nature of the heavy and light strand synthesis and the very large number of base pair repeats which mismatch during replication and result in mtDNA deletions.…”

“…We have earlier reported that coenzyme Q 10 functions in the process of gene regulation (Linnane et al 2002a;Linnane 2002b). This conclusion arose from administering coenzyme Q 10 in a placebo controlled trial to patients for a period of 4 weeks prior to undergoing hip replacement surgery.…”