卷 53, 编号 4 (2017)

Protein phosphotyrosine phosphatase 1B (PPTP1B) dephosphorylates receptor and nonreceptor forms of tyrosine kinases, causing the inhibition of their activity and thus regulating appropriate signaling cascades. Increased PPTP1B activity leads to insulin and leptin resistance, being among the causes of type 2 diabetes mellitus and many other metabolic and functional disorders. Selective PPTP1B inhibitors normalize functions of insulin, leptin and some other systems comprising different forms of tyrosine kinases as signaling components, and their development is a promising approach to treat and prevent metabolic disorders. Currently, an active search is in progress for “binary” PPTP1B inhibitors able to interact simultaneously with the catalytic and allosteric sites of the enzyme, providing thereby high efficiency and selectivity of their action. This review focuses on the status quo of the problem of studying the structure, functions and regulatory properties of PPTP1B, its role in the development of metabolic disorders, as well as on recent advances in designing selective PPTP1B inhibitors.

Activity of antioxidant enzymes (superoxide dismutase and catalase) and low molecular weight antioxidants (tocopherol and retinol) was studied in tissues of 8 semiaquatic mammalian species. In animals from different taxa, the enhancement of antioxidant defense can be achieved either by increased enzymatic activity of tissues or elevated concentration of low molecular weight antioxidants. The level of enzymatic and nonenzymatic (low molecular weight) antioxidants, determined in tissues and organs of diving mammals, is likely to be considered as an integral complex, which has evolved to ensure the greatest efficiency of metabolic systems during adaptation to species-specific habitats.

In in vitro experiments, interspecies differences were revealed in the erythrocyte responses in varied rodent species—laboratory mice (Mus musculus L.), tundra voles (Microtus oeconomus Pall.) and bank voles (Myodes glareolus Pall.)—to the effect of chemical agents able to interact with membrane lipids and disrupt the membrane structure (detergent Triton X-100, oxidative stress inductor AAPH, antioxidant ionol or BHT, uranyl ion). It was hypothesized that these differences are due to physicochemical peculiarities of the erythrocyte membrane structure, specifically, the ratio of choline-containing fractions of phospholipids (phosphatidylcholine and sphingomyelin). The use of blood erythrocytes as an in vitro experimental model to study the mechanisms of toxicity as well as antioxidant and membrane-protective properties of compounds of different nature was shown to imply the choice of an adequate source of erythrocytes in view of considerable speciesdependent structural specificity of the lipid component of mammalian erythrocyte membranes.

Using a behavioral approach, it was shown that stereoisomers and other derivatives of amino acids (Ala, Glu, Gln; 0.1–0.01 М) have different palatability to fish (three-spined stickleback Gasterosteus aculeatus). The palatability of L-α-Ala is higher than of D-α-Ala or L-β-Ala, however, L-Glu and D-Glu equally increase the uptake of agar-agar pellets. L-Glu-Na has no stimulatory effect, probably, due to carnivorous feeding type in the three-spined stickleback. Palatabilities of L-Gln and L-Gln-HCl differ considerably. It is assumed that the influence of the configuration and structure of molecules on the palatability of amino acids to fish, as well as their taste preferences, are species-specific. The diversity of taste properties not only of L-, but also D-isomers of amino acids may matter in choosing adequate food objects in fish. Fish feeding behavior during oral sensory testing of artificial pellets, containing amino acids or their derivatives, obeys two alternative stereotypes, differing in the number of repeated manipulations with pellets and duration of the pellet retention time.

Activity of sensorimotor cortical neurons in the ground squirrel was studied on slices under cooling the incubation medium from 32–34 to 21–26°С. Hypothermia evoked spontaneous firing activity in “silent” neurons and a slight decrease in firing in high-frequency neurons. Changes in the firing rate arose below 27°С and were accompanied by a fall in the spike amplitude. The intensity of hypothermic and post-hypothermic changes in ground squirrels was lower than in guinea pig sensorimotor cortical neurons recorded under the same conditions. In ground squirrels, most hypothermia-resistant were high-frequency (more than 8 spikes/s) neurons, which accounted for 45% of the recorded, while in guinea pigs high-frequency neurons occurred only in 15% of records. By the diameter of cell bodies, the population of sensorimotor cortical neurons was more homogeneous in ground squirrels than in guinea pigs. It is suggested that specific hypothermic changes in sensorimotor cortical neurons of ground squirrels relate to a lower density of K⁺ channels in their plasma membranes, because in the mammalian nervous system the latter open below 27°С due to thermal limitations of the M-cholinergic reaction which blocks these channels.