THE BASIC ROLE OF THE PROCESSES WITH INVOLVEMENT OF REACTIVE OXYGEN SPECIES IN LIVING FUNCTIONS REGULATION.
V.L. Voeikov
Lomonosov Moscow State University, Moscow
Reactive oxygen species (ROS), the products of one-electron oxygen reduction, are represented by superoxide anion radical (O2·¾), H2O2, hydroxyl radical (OH·), hydroperoxides (ROOH), and their radicals (ROO·). They are able to initiate uncontrolled chain processes in which multiple organic molecules are involved. Reactions of ROS are up to 10-fold more exergonic than ordinary biochemical reactions. ROS interact non-specifically with many organic molecules. Due to all these properties ROS are extremely strong oxidants and in contemporary biochemistry paradigm they are considered to be the universal pathogens. Their generation in living systems is looked upon as grievous though inevitable price for aerobic respiration that had emerged in the course of the evolutionary process consequently to the appearance of atmospheric oxygen – the by-product of plant photosynthetic activity.
However this concept ignores a lot of hard evidence showing that ROS are absolutely necessary for normal vital activity. If air is deficient of superoxide anions (Chizhevsky’s «air ions») human beings and animals become sick and can even pass away. On the other hand, more than 10-15%, and under the special conditions up to 30% of oxygen consumed by animals goes to ROS production. ROS are continuously generated in our body by ubiquitous specialized enzymes, by the enzymes performing other primary functions, and also non-enzymatically. Thus, ROS should play rather important physiological functions.
Living cells are known to react to external stimuli in one of the following ways: they either perform their specialized function, or change their specialization (differentiate or dedifferentiate), or proceed into the mitotic cycle, or, finally, proceed into the so called «programmed cell death» – apoptosis. It turns out that in most cases ROS determine the outcome of cell reaction upon specific extracellular biomolecular regulators. Besides, ROS themselves may imitate the action of certain hormones, neurotransmitters, cytokines upon particular cells. Biomolecular regulators may, in their turn, modulate ROS production by the cells. Thus, ROS may be looked upon as universal information messengers. But if ROS are devoid of specificity attributed to biomolecular regulators, how can they provide a precise regulation of cellular functions?
Though a considerable part of consumed oxygen is used in the organism for ROS production, the average levels of free radicals and other ROS in cells and extracellular fluids are extremely low. The so called «antioxidants» of enzymatic and other nature set a very high rate of their recombination and transformation into another compounds. Thus very slight variations in the rates of ROS production and/or consumption may result in drastic spikes and oscillations of their immediate levels. It should be stressed that the processes of ROS metabolism, and in particular the reactions of their recombination are accompanied by the generation of electron excited states. Our and other authors’ results suggest that due to cytoplasm organization energy of electron excitation is unlikely to dissipate into heat. Rather it may accumulate in molecular and supramolecular ensembles, and redistribute among them by radiative and radiation-less routs providing intracellular and intercellular cooperation. How can it be done?
Is more and more recognized that biological reactions proceed as non-linear oscillatory processes. In particular, as we and others have shown the processes involving ROS are oscillatory as a rule. We speculate that the mechanisms of biological action of ROS are dependent upon the structure of the processes in which they participate, rather than upon the mean concentrations of these particles. By the «structure of the processes» we imply the frequency-amplitude patterns of the reactions of ROS recombination and their interactions with other partners, taking into consideration that these processes supply energy of activation for the numerous specific biochemical reactions. Periodic as well as non-linear oscillations emerge in the processes of ROS metabolism, but they decay without re-priming with periodic external signals. Hence, for the effective ROS production the organism should be «sparked» from the outside. «Sparks» may come in the form of air- or hydro-ions (external O2·¾), or by virtue of ROS generation in its aqueous medium by high energy photons (UV- and lower short-wave range), or by beta-particles produced by of 14С and 40К, that represent natural redioactivity in all the organisms.
Oscillations that arise in the course of ROS metabolism in the organism, and that in their turn determine and/or modulate the rhythms of biochemical and physiological processes are more or less dependent upon certain external oscillators, in particular upon oscillations of external EM- and magnetic fields. ROS reactions may be very sensitive to their influences, because they are intrinsically the processes of electron transfer in electron-excited media. Such processes, as it follows from the current concepts of the physics of non-linear autostochastic systems are highly sensitive to weak resonance interactions.
Let us consider now how ROS can regulate biological functions at the level of the whole organism. It is well known that blood neutrophils can efficiently generate ROS, which in this case are considered to be used for virus and bacteria «burning out». However, шt turns out that lymphocytes and trombocytes, that do not participate in direct elimination of microbes also produce ROS. Fibroblasts, endothelial and smooth muscle cells also possess highly active ROS-generating enzymes. ROS production by connective tissue, to which both blood and «ordinary» connective tissues belong is of particular interest in the light of presumed energy-informational role played by ROS metabolism. ROS are generated not only by cellular elements of connective tissues, but also by extracellular proteins (though in the latter case at much lower rate). Plasma proteins and collagen become sources of ROS due to their glycoxidation (Maillard reaction). It should be stressed that all the collagens and many plasma proteins have fibril helix structure and are able in principle to transfer EM-waves for long distances. It is interesting to speculate that extracellular connective tissue elements perform besides their structural function another important role in all the organisms – the role of channels for information transfer that join together all the tissues and organs and that also expose to the periphery (say, in the form of acupuncture points). Cellular elements of connective tissues play in this case the role of re-translators, decoders and amplifiers of the incoming signals. Needless to say that all the living things possess connective tissues or their analogs even if they are devoid of blood and nervous systems.
If ROS play such a fundamental role in vital functions of all the organisms, they should play it throughout the evolutionary process. But it is a common knowledge that free oxygen appeared due to photosynthetic activity of green plants, and that the long period of living forms evolution was anaerobic. It should be pointed out that this «knowledge» is just the plausible speculation, while the direct experiments demonstrate now that under the influence of such common factors as sound, filtration, freezing-thawing, ets., water may be broken down to hydrogen atoms and oxygen radicals, the latter recombine to form hydrogen peroxide that eventually gives birth to molecular oxygen. Estimates show that the rates of these reactions are such as to provide atmospheric oxygen building up to concentration similar to the current level within only several hundred thousands of years. If so, than the development of organic life on Earth was taking place in the presence of free oxygen and its reactive species from the very beginning. Needless to say that the structure of the processes of abiogenic ROS metabolism was under the control of the external EM- and magnetic fields of cosmic and terrestrial origin. Undoubtedly, the processes involving ROS are not exclusive «antennas» for external regulatory signals. However, if for some reasons these processes deteriorate or fade away in the particular individual living system, its internal informational flows may suffer to such an extent that it loses its integrity and ability to receive external information by any other means.