[Phenotypic characteristics of factor expression induced by hypoxia and redox status of the rat neocortical cells at different stages of adaptation to hypoxia].

Hypoxic preconditioning induces two-phase increase of HIF-1alpha expression in the neocortex of low-resistance rats. The first, brief phase appears after each hypoxic episode and rapidly disappears in normoxic conditions. The second increase in of HIF-1alpha expression occurs in 24 hours after the hypoxic episode. The phase-nature of HIF-1alpha expression corresponds to the dynamics of urgent and long-term resistance in low-resistance rats, which suggests the HIF-1alpha involvement in mechanisms of urgent and long-term adaptation. It was found that in the mode of preconditioning, hypoxic treatments mobilized the anti-oxidant system (activated Cu, Zn-SOD) and had no effect on the intensity of lipid peroxidation processes in neocortex (INH, 10% O2) or even decreased the content of lipid peroxidation products and oxidized glutathione in neocortical cells in the early post-hypoxic period (HBH-5000, 10.5% O2). Thus, ROS do not play a key role in the induction of HIF-1alpha expression and fast-response/long-term adaptation to O2 deficiency in hypoxia-sensitive animals. In high-resistance rats, hypoxia preconditioning does not influence the HIF-1alpha protein expression and the adaptation. Severe hypoxic modes (HBH-7000, 8% O2) caused activation of lipid peroxidation processes in neocortex of hypoxia-sensitive rats. With the pro-oxidant systems dominating over the anti-oxidant ones, the neocortical expression of HIF-1alpha was found to decrease, which was accompanied by the impairment of the mechanisms of fast-response/long-term adaptation to hypoxia.

[Effect of hypoxia on dynamics of HIF-1alpha level in the cerebral cortex and development of adaptation in rats with different resistance to hypoxia].

Hypoxic preconditioning induces two-phase increase of HIF-1alpha expression in the neocortex of low-resistance rats. The first, brief phase appears after each hypoxic episode and rapidly disappears in normoxic conditions. The second increase in of HIF-1alpha expression occurs in 24 hours after the hypoxic episode. The phase-nature of HIF-1alpha expression corresponds to the dynamics of urgent and long-term resistance in low-resistance rats, which suggests the HIF-1alpha involvement in mechanisms of urgent and long-term adaptation. In high-resistance rats, hypoxia preconditioning does not influence the HIF-1alpha protein expression and the adaptation. Severe hypoxia inhibits the HIF-1alpha protein expression in the neocortex of both rat phenotypes, depresses the formation of urgent resistance, and abolishes the induction of long-term adaptation.

[Biochemical basis of the single theory of aging. Part II. The cell aerobic status, the hypoxia resistance and proliferation].

Cells of an organism have different parameters of morphology, metabolism, isoenzyme composition, proliferation and respiration. These differences are derivatives of the cell aerobic status. The primary oxygen acceptors are the "macroscopic" cells (neurons, cardiocytes). In these obligatory aerobic cells oxygen is converted into metabolic water directly by the cytochrome oxidase activity. The secondary oxygen acceptors are the "microscopic" cells (other single-nucleus cells). In these facultative aerobic cells oxygen is converted into hydrogen peroxide. The intracellular labile peroxide pool of oxygen is formed by the oxidase, cytochrome P450, superoxide dismutase, and the mitochondrial cyan-resistance oxidase. The mitochondrial isoenzymes of catalase, glutation peroxidase, and thioredoxin reductase convert hydrogen peroxide into molecular oxygen and form high local oxygen concentration as the major factor for the cytochrome oxidase activity. The hypoxia resistance is increased by the growth of the functional activity of the peroxide-generative and peroxide-mobilizative enzyme systems.