Abstract
The plenary session was opened by the deputy director of I. Pavlov Institute of Physiology (St. Petersburg, Russia) Professor M.O. Samoylov who presented the review of hypobaric hypoxic preconditioning signal mechanisms including key intracellular regulatory systems, early genes, families of inducible and activation transcription factors, pro-adaptive proteins which are consistently involved in the development of initiation, induction, and expression of hypoxic tolerance. It was emphasized that essential selection of an optimal hypoxic preconditioning regimen is necessary for the effective activation of neuroprotective signaling pathways. Two satellite reports from this institute were devoted to hypoxic post-conditioning as a new effective strategy for the correction of hypoxic and other stress disorders.
Another plenary lecture was made by Professor V.N. Ilyin (Ukrainian National Institute of physical training, Kiev, Ukraine): “Genetic markers of physical and hypoxic tolerance in different sports”. Using meta-analysis of scientific publications, it is possible to identify specific gene candidates that could mostly affect physical capacity in different types of physical activity. Thirty-four genes were identified in a human genetic map which represented the predisposing to the development of certain physical traits, for example, physical endurance or speed-strength qualities. The distribution of allelic variants Pro582–>Ser polymorphism in HIF-1alpha gene of power-orientated athletes was also shown. This provides a selection to certain professional sports. However, new genetic achievements generate great ethical and social problems.
Professor I.N. Mankovska (Bogomoletz Institute of Physiology, Kiev, Ukraine) presented data about changes in the expression profile of oxygen-dependent genes during adaptation to hypoxia. Role of HIF-3α was shown using the administration of interfering RNA to this subunit, as well as the role of HIF-coactivators recruitment system, HIF target genes (EPO, EPOR, GLUT-1, GLUT-4), gene antioxidant control, and mitochondrial biogenesis (mRNA expression of antioxidant enzymes, nuclear respiratory factor-1, and pyruvate dehydrogenase kinase-1).
Y.I. Kirova and L.D. Lukyanova of Moscow showed that after hypoxic preconditioning the two-phase dynamics of HIF-1α expression is formed in low hypoxia-resistant animals. The first maximal expression is accompanied by a decrease in its proteosomal degradation and increase in its oxygen-independent synthesis under the control of PI3K and MAPK signal pathways. The second maximal HIF-1α expression is formed after 24 hours of reoxygenation due to a decrease of its degradation in prolyl-hydroxylase reactions. The relationships between HIF-1α expression and the duration of hypoxic load, as well as the differences between high- and low-resistant animals were discussed.
Many presentations were devoted to ischemic/reperfusion consequences. A.G. Portnychenko (Kiev, Ukraine) demonstrated that hypoxic preconditioning attenuated reperfusion damage of rat cardiomyocytes with reducing the release of lactate dehydrogenase (LDH) by 27.6%. After ischemia and reperfusion, expression of 5-lipoxygenase (5-LO) was 10.5-fold elevated in the left ventricle and 14.3-fold in the right one. During ischemia/reperfusion, gradual translocation of 5-LO protein occurred in the nuclear subcellular compartment, more expressive in the left ventricle. Hypoxic preconditioning did not significant increase 5-LO expression but fully prevented its growth in the following ischemia-reperfusion and partly reduced protein translocation at reperfusion in the left ventricle. Thus, hypoxic preconditioning limits proinflammatory effects of ischemia/reperfusion in myocardium, preventing the increase in 5-LO expression and reducing the cardiomyocytes alteration.
T.M. Kovalenko and colleagues (Kiev, Ukraine) investigated the neuroprotective effects of hypoxic preconditioning on pyramidal neurons of CA1 hippocampal area in Mongolian gerbils after global cerebral ischemia. Activation was observed of microglial cells that are able to eliminate the negative ischemia effects and stabilize the state of neurons. Significant increase in MnSOD activity in neurons of preconditioned animals was revealed a day after ischemia/reperfusion, suggesting the activation of long-lasting mechanisms of endogenous neuroprotection.
Another work from the Bogomoletz Institute of Physiology (V.S. Nagibin et al.) was devoted to the role of proteasomal proteolysis in the pathogenesis of ischemia-reperfusion damage in cardiomyocytes. Preliminary inhibition of proteasomal proteolysis had a significant impact on the implementation of preconditioning. The other investigation from this lab (M.A. Kuzmenko, et al.) has shown different levels of natriuretic genes expression after coronary and noncoronary ischemic damage: in the first case NPPB and NPR-A gene expression increased in 83 and 16 times, whereas NPPA and NPR-C expression decreased in 11 and 6 times, respectively; in the second case the level of mRNA genes NPPB and NPR-A increased only in 4 and 1,5 times, respectively. So, the intensity of response of cardiac cells genetic apparatus on coronary and noncoronary damage is significantly different.
Many reports were devoted to different aspects of intermittent hypoxia training/treatment (IHT). Professor A.V. Abramov (Zaporozhye, Ukraine) showed that 2-week IHT caused a 56% increase in the square of rat pancreatic islets and 68% augmentation of β-cells content mostly due to the two-fold decrease of B-endocrinocyte apoptosis. The positive effect was preserved at least for 10 days. Another investigation on a streptozotocin type 1 diabetic rat model proved that IHT decreases blood glucose content by 16%, increases the insulin accumulation index in the pancreas by 25%, and blood insulin content by 40%. The IHT glucose-lowering effect was also confirmed on patients with diabetes mellitus (Yu. M. Kolesnik, et al.).
Professor T.V. Serebrovska of Kiev gave a talk “How different IHT modalities influence tissue oxygenation and mitochondrial metabolism.” Effects of the five most widespread modes of normobaric hypoxic training on rat muscle PO2 and mitochondrial respiration were compared. The most effective IHT regimen was 5 min 12% O2 and 5 min air breathing, five cycles per day for 2 or 3 weeks, depending on the task of IHT.
In the session “Population genetics” G. Portnichenko of Kiev spoke on the insulin-like growth factor-1 (IGF-1) in residents of Elbrus region. Expression of IGF-1 and leptine was reduced in highlanders as compared to sea-level residents. Studies revealed intensified carbohydrate utilization for energy supply and switch to increased lipid substrate consumption in highlanders with accompanied decreasing of leptine synthesis and energy expediture. M.I. Kitaev and K.A. Saburov of Bishkek (Kirgizia) provided HLA-antigen typing in Tien Shan residents at different altitudes. Frequency of different genes and haptens occurrence was described.
Many other presentations deserve consideration. The conference ended with a round table on “Fundamental and applied significance of genetic achievements in the field of hypoxia.”