Original ContributionsEffects of coenzyme Q10 and α-tocopherol administration on their tissue levels in the mouse: elevation of mitochondrial α-tocopherol by coenzyme Q10
Introduction
Coenzyme Q (CoQn) is a redox-active quinone derivative with a variable number of isoprene units, ranging from seven to twelve in different species [1]. It is present in virtually all the cellular membranes. In mammals, such as the mouse and the rat that have relatively high metabolic rates and short life-spans, CoQ9 is the predominant homologue, whereas in the long-lived mammals, such as the cow and humans with relative low rates of metabolism, CoQ10 is the predominant homologue [2]. The most recognized physiological function of CoQ is the transfer of electrons in the mitochondrial respiratory chain from complex I and II to complex III and the translocation of protons across the inner mitochondrial membrane [3], [4]. Autoxidation of mitochondrial CoQ (ubisemiquinone) has also been demonstrated to be the major intracellular source of O2−• and consequentially other potentially deleterious reactive oxygen species, derived from O2−• [5], [6], [7].
More recently, CoQ has been postulated to also act as a potent antioxidant. Studies in this laboratory [8] and others [9], [10], [11] have indicated that the antioxidative role of CoQ involves an interaction with α-tocopherol, a well recognized antioxidant in the membranes. Furthermore, it has been demonstrated that α-tocopherol reacts with peroxyl [12] as well as superoxide anion radicals [13], becoming a tocopheroxyl radical [14], that, in respiring mitochondria, can react with reduced CoQ (ubiquinol) to regenerate α-tocopherol [15]. The existence of such a recycling mechanism has led to the postulate that in respiring mitochondria, CoQ has a sparing effect on α-tocopherol [8], [10]. Whether such a mechanism is also operative in vivo is currently unknown. Indeed, one of the objectives of the present study was to determine whether CoQ has a similar sparing effect on α-tocopherol in mitochondria in vivo. If the hypothesis that CoQ spares α-tocopherol is indeed valid, experimental augmentation of CoQ should result in an elevation of mitochondrial α-tocopherol, but not the vice versa.
Quite obviously, the experimental design of such a purported study would necessarily entail the administration of exogenous CoQ to the experimental animals. However, such a procedure would also pose two potential difficulties. The first is that the readily available homologue of CoQ is CoQ10, whereas the predominant CoQ homologue in the rodents is CoQ9. To achieve elevation in the levels of CoQ9 in the mouse, a conversion of the experimentally administered CoQ10 to CoQ9 would necessarily have to occur systemically. Secondly, most of the studies in the literature, often involving relatively short-term administration of CoQ10, have indicated that dietary supplementation results in an increase in CoQ content in the liver, spleen and serum, but not in other tissues [16], [17], [18], [19], [20]. Nevertheless, recently Matthews et al. [21] reported that the concentration of CoQ9 in the rat brain can be augmented experimentally in relatively old animals after a prolonged period of CoQ10 administration.
The finding by Matthews et al. [21] has important functional implications because of the complicated physiological roles played by CoQ. As indicated above, CoQ is not only a vital substance, but it can also be potentially harmful due to the generation of O2−• by CoQ autoxidation. Furthermore, it is well known, at least anecdotally, that a considerable number of humans are using CoQ10 as a dietary health adjuvant. Thus, an additional purpose of this study was to determine whether CoQ levels can be increased experimentally in a species other than the rat and if so in which particular tissues. Furthermore, because of the suspected interaction between CoQ and α-tocopherol, it was also determined whether the intake of α-tocopherol alone or together with CoQ also results in an elevation of its content in various tissues.
Section snippets
Materials
All solvents used were of HPLC grade (Fisher Scientific, Fair Lawn, NJ, USA). Ubiquinone-9, ubiquinone-10, (±)-α-tocopherol, and α-tocopherol acetate were purchased from Sigma (St. Louis, MO, USA). Ethylenedinitrilo-tetraacetic acid disodium salt dihydrate (EDTA) was obtained from Fisher Scientific. Ubiquinol-9 and ubiquinol-10 were prepared by the reduction of corresponding quinones with sodium borohydride (Sigma, St. Louis, MO, USA), as described by Takada et al. [22].
Animals
A total of 49 male
Results
Four different groups of 24-month-old mice were experimentally administered CoQ10 alone, or α-tocopherol alone, or CoQ10 and α-tocopherol together, or soy-bean oil (control) for 13 weeks, after which the amounts of α-tocopherol and coenzyme Q homologues (CoQ9 and CoQ10) were measured in: (1) serum; (2) homogenates of the brain, heart, kidney, liver and upper hindlimb skeletal muscle; (3) mitochondria from these tissues; and (4) brain synaptosomes.
Discussion
The main findings of this study are (1) Experimental administration of α-tocopherol resulted in an increase in α-tocopherol concentration in virtually all the tissues of the mouse, albeit the magnitude of the increase varied in different tissues; (2) CoQ10 administration resulted in an increase in its amount only in the serum, liver homogenate, liver mitochondria, and kidney mitochondria, but not in the homogenates or mitochondria of brain, heart or skeletal muscle; (3) CoQ10 intake caused an
Acknowledgements
This research was supported by the grant RO1 AG13563 from the National Institutes of Health-National Institute on Aging.
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