Begell House Inc.
International Journal of Physiology and Pathophysiology
IJPP
2155-014X
1
4
2010
Cardioprotective Effects of ATP-Sensitive Potassium Channels Activation in Experiments in Vivo: Influence on Biochemical Parameters of Blood Following Ischemia-Reperfusion of Myocardium
305-313
10.1615/IntJPhysPathophys.v1.i4.10
Ruslan B.
Strutynskyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Anatoliy V.
Kotsuruba
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Oleksander P.
Neshcheret
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Angela N.
Shysh
Palladin Biochemical Institute, NAS of Ukraine, Kyiv
Roman A.
Rovenets
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Oleksiy O.
Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
KATP channels
flocalin
ischemia-reperfusion
free radicals
NO system
In experiments on the anesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min), participation of biochemical processes in the cardioprotective effect of the preischemic activation of ATP-sensitive potassium (KATP) channels caused by intravenous introduction of flocalin, a new fluorine-containing opener of these channels was shown. Flocalin was introduced in a dose of 0.1 mg/kg of animal body weight which practically did nit change parameters of hemodynamic under normoxia. Thus, experiments on the influence of flocalin on changes of biochemical parameters of arterial blood during ischemia-reperfusion of myocardium revealed certain features of ischemia-reperfusion syndrome development under stimulation of KATP channels. Analysis of blood biochemical parameters revealed that flocalin suppressed free radicals reactions and manifested anti-oxidative properties: reduced quantity of H2O2 and NO3− (the latter can be interpreted as a reduction in peroxini-trite formation), prevented the decline of catalase and superoxide dismutase activity. Practically constant content of low-molecular nitrosothiols in blood during the whole experiment and increase in the level of NO2− during the reperfusion can be indicative of intact functions of the NO system and protective influence of flocalin during the ischemia-reperfusion of myocardium. Practically the unchanged content of inorganic phosphorus and uric acid in blood during ischemia-reperfusion under conditions of preischemic introduction of flocalin indicates that there is a prevention of ATP degradation and formation of both superoxide anion by xantinoxidase and peroxinitrite by its interaction with nitric oxide. All the mentioned properties of flocalin, related with the changes in biochemical parameters of arterial blood, together with the changes in hemodynamic parameters, result in decrease of infarct size in myocardium after ischemia-reperfusion by 37% versus control experiments.
The Association of A−1082→G Polymorphism of IL-10 and (A−308→G) Polymorphism of TNFα Genes with Bone Density in Elderly Women
315-327
10.1615/IntJPhysPathophys.v1.i4.20
Iryna M.
Pishel
Institute of Gerontology of the Medical Academy of Sciences of Ukraine, Kyiv
Olga O.
Yevtushenko
Institute of Gerontology of the Medical Academy of Sciences of Ukraine, Kyiv
Yuriy I.
Leonov
Institute of Gerontology of the Medical Academy of Sciences of Ukraine, Kyiv
Nataliia V.
Grygorieva
Chebotarev Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Ukrainian Scientific-Medical Center of Osteoporosis, Kyiv, Ukraine
Tatiana V.
Orlyk
Institute of Gerontology of the Medical Academy of Sciences of Ukraine, Kyiv
Dmytro V.
Shytikov
Institute of Gerontology of the Medical Academy of Sciences of Ukraine, Kyiv
Vladyslav V.
Povoroznyuk
Chebotarev Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Ukrainian Scientific-Medical Center of Osteoporosis, Kyiv, Ukraine
Gennadi M.
Butenko
Institute of Gerontology; and Institute of genetic and regenerative medicine AMN of Ukraine, Kyiv
gene polymorphisms
bone
aging
IL-10
TNFalpha
We studied the association between bone mineral density and (A −1082→G) polymorphism of IL-10 and (A−308→G) polymorphism of TNFα genes. SNP-polymerase chain reaction was used. The study failed to find significant association of A−308→G TNFα polymorphism and bone state in postmenopausal women. The patients with AA genotype of A−1082→G IL-10 gene have significantly lower indices of bone mineral density comparing with G allele carriers (GG/AG). This association remained true for data of bone mineral density of total body, and separate parts of skeleton: lumbar spine, femoral neck, Ward's triangle of total femur. Our study indicates that A−308→G polymorphism of TNFα gene is not associated with indices of bone mineral density in postmenopausal women. However, there is strong evidence that women, carriers of AA genotype of A−1082→G polymorphism of IL-10 gene have significantly lower indices of bone mineral density. This indicates the potential for predictive genetic testing of osteoporosis risk. Analyses of gene combination IL-10 G−1082→G and TNFα G−308→G ('antiinflammatory genotype') did not show any significant association of this genotype with bone characteristics, which shows low predictive value of this combination for diagnostics of osteoporosis.
The Effect of Neuraminidase Blocker on Gabazine-Induced Seizures in Rat Hippocampus
329-334
10.1615/IntJPhysPathophys.v1.i4.30
Alina V.
Savrasova
Bogomoletz Institute of Physiology, Kiev
Irina V.
Lushnikova
O.O. Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Olena V.
Isaeva
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Galina G.
Skibo
A. A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Dmytro S.
Isaev
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Platon G.
Kostyuk
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
polysialic acid
neuraminidase blocker
seizure
gabazine
hippocampus
Concentration of neuraminidase (NEU), an enzyme which cleaves negatively charged sialic acids from carbohydrate moieties of the cellular membrane, could vary depending on physiological conditions. Multiple evidences suggest that fluctuations of NEU extracellular concentrations can influence neuronal activity. In the present study we have examined the effect of down regulation of endogenous NEU activity on seizure-like activity (SLA) induced by gabazine (specific blocker of inhibitory synaptic transmission) in the hippocampal CA1 pyramidal region of cultured slices. We have shown that in slices pretreated with the blocker of endogenous NEU (N-Acetyl-2,3-dehydro-2-deoxyneuraminic acid, NADNA) duration of synchronous oscillations induced by gabazine was considerably increased comparatively to control untreated slices. This study adds further information that changes in the level of NEU activity is an important factor, which can affect neuronal network excitability.
Effects of Genipin at NO synthesis and Ischemia-Reperfusion Induced Oxidative Stress in Old Rat Hearts
335-344
10.1615/IntJPhysPathophys.v1.i4.40
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Yulia V.
Goshovska
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Yulia P.
Korkach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Tetyana V
Shimanskaya
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Anatoliy V.
Kotsuruba
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
ischemia-reperfusion
oxidative stress
genipin
nitric oxide synthase
aging
uncoupling proteins
heart
Genipin is aglycone of genipiside, one of the active compounds of Gardenia gasminoides Ellis. The gardenia fruit extract has been used in traditional Chinese medicine to relieve the symptoms of type 2 diabetes which is accompanied by extensive oxidative stress and endothelial dysfunction of NO production. Besides, genipin was shown to inhibit UCP-dependent proton leak through the inner mitochondrial membrane, which leads to the increased mitochondrial potential and ATP production. We have studied the effects of genipin at ischemia/reperfusion-induced oxidative stress and activity of NOS isoenzymes using Langendorf perfused old rat heart model. Ischemia-reperfusion is a well known oxidative agent, which induces significant increase in superoxide radical, hydrogen peroxide and hydroxyl radical content. Genipin administration in a dose of 10−5 M for 15 minutes before the prolonged ischemia exerted powerful antiradical and antilipoperoxidative effects. Heart ischemia-reperfusion was accompanied by generation of peroxinitrite and by nitrozative stress. We have demonstrated the inhibitory impact of genipin on iNOS expression, which is possibly, occurs via preoteinkinase A inhibition and via stabilization of I-κB-NF-κB complex. Genipin stimulated cNOS activity perhaps by activating PI3K/Akt signaling pathway. Although, post-ischemic recovery of cardiodinamic parameters of old rat hearts was depressed due to the "switch of" of the NO production by inducible NOS, which is important in early period of reperfusion. Thus, we conclude that genipin is a powerful antioxidant and it processes an insulin-like activity due to its ability to manage NO production at the level of intracellular signaling cascades.
Age-Dependence in Alterations in Nitric Oxide Synthesis in Cardiovascular System during Adaptation to Physical Training
345-356
10.1615/IntJPhysPathophys.v1.i4.50
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Olga V.
Bazilyuk
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Anatoliy V.
Kotsuruba
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Lyubov G.
Stepanenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Sergiy O.
Talanov
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
Yu. P.
Korchak
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv
nitric oxide
vascular tone
endothelium
precondition
training
aging
Emerging evidence suggests that training-derived cardiovascular preconditioning is mediated by antiapoptotic and antioxidant action of nitric oxide. Nitric oxide has been reported as one of the major down-regulator of ROS generation and apoptosis-mediated cardio-vascular dysfunction in aging animals and man. We studied both activity of oxidative de novo and nonoxidative salvage pathways of nitric oxide synthesis and nonoxidative L-arginine degradation by arginase. Our results show (1) the activation of both salvage (by nitratereductase + nitritereductase reduction of nitrate-and nitrite-anions) and de novo (L-arginine oxidation by NOS) pathways of nitric oxide synthesis and (2) rising of nitric oxide bioavailability in training rats. (3) Salvage/ de novo ratio degree in aorta correlate with aortal reactivity to dilation action of nitric oxide suggests that degree of this ratio in plasma can be a potent biochemical marker of training effectively in sportsmen. In aging rats endothelial dysfunction is not eliminated by training, but long-time swimming (as preconditioning) increased endothelial (NO) -dependent vasodilatation of the aortal VSMC of both adult and aging rats. Thus, training-dependent vaso-protection in adult and aging rats can be released by up-regulation of NO synthesis, especially by nonoxidative salvage, but not by oxidative de novo pathways.
Action of Nitrogen Oxides and Hydrogen Peroxide on Ca2+ Transport in Sarcoplasmic Reticulum of Permeabilized Myocytes of Utera
357-365
10.1615/IntJPhysPathophys.v1.i4.60
Yuriy V.
Danylovych
Palladin Institute of Biochemistry, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
nitrogen oxide
hydrogen peroxide
calcium
sarcoplasmic reticulum
utera
Investigations were conducted on a model of digitonin-permeabilized myocytes from pig uterus using 45Ca2+. We have established that in the presence of 10 mM of sodium azide, which reliably represses the energy-dependent accumulation of Ca2+ in mitochondria, sodium nitroprusside (10 μ;M − 0.1 mM), nitrite-anion (0.1 μ;M − 10 μ;M) and hydrogen peroxide (0.1 μ;M − 10 μ;M) stimulated energy-dependent introduction of Ca2+ in sarcoplasmic reticulum. When studying processes of passive Ca2+ release from this pool, which was preliminary accumulated in the ATP-dependent process, we have discovered that administration of sodium nitroprusside (10 μ;M), nitrite-anion (10 nM − 0.1 mM) and hydrogen peroxide (10 nM) resulted in the decline of passive Ca2+ release, while 0.1 mM of H2O2 resulted in the opposite effect. These findings allow us to assume that the tested chemicals can reduce Ca2+ concentration in the myoplasm, and hence, the contractile activity, acting on the level of sarcoplasmic reticulum.
Increased Expression of Voltage-Dependent Anion Channel and Adenine Nucleotide Translocase and the Sensitivity of Ca2+-Induced Mitochondrial Permeability Transition Opening Pore in Old Rat Heart
367-375
10.1615/IntJPhysPathophys.v1.i4.70
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Nataliya A.
Strutynska
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Snizhana V.
Chorna
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
Viktor E.
Dosenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Galyna L.
Vavilova
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
voltage-dependent anion channel expression
adenine nucleotide translocase
mRNA expression
mitochondrial permeability transition pore
heart
aging
We have investigated mRNA and protein expression of voltage-dependent anion channel (VDAC), mRNA adenine nucleotide translocase (ANT) as well as the sensitivity of the mitochondrial permeability transition pore (MPTP) to Ca2+ in the adult and the old rat heart. It was shown that in the old rats' hearts VDAC mRNA expression increased by 1.7 (P < 0.05) times and mRNA ANT expression increased 1.8 (P < 0.05) times in comparison with adult animals. Western Blot analysis has shown that the level of the VDAC protein expression in old rats' hearts also significantly increased as compared with adult animals. In old rats' hearts sensitivity of MPTP opening to calcium (10−7 − 10−4 M) determined by mitochondria swelling increased two-fold (P < 0.05). Therefore, an increased VDAC and ANT expression, as the main structure-functional components of the MPTP, and an increased sensitivity of MPTP opening to Ca2+ caused an increase in mitochondrial membranes' permeability in aging. Each of these factors may contribute to alterations in mitochondrial barrier properties and lead to mitochondrial dysfunction.
Influence of Intermittent Hypoxic Training on Hemodynamic Effects of NOS-1 Activation in Medullary Cardiovascular Neurons in Rats
377-388
10.1615/IntJPhysPathophys.v1.i4.80
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Lyudmila M.
Shapoval
Bogomolets Institute of Physiology, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
Lyudmila S.
Pobegaylo
Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv
Lyubov G.
Stepanenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Olga V.
Dmytrenko
Bogomolets Institute of Physiology, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
Vitali O.
Bouryi
Laboratory of Molecular Pharmacology and Biophysics of Cell Signalling, Bogomoletz Institute of Physiology, Kiev, Ukraine
intermittent hypoxic training
neuronal NO-synthase
medullary cardiovascular neurons
In our experiments, male Wistar rats, weighing 300 ± 40 g, were exposed to intermittent hypoxia in a special chamber by its ventilation with hypoxic mixture containing 12% O2 in N2 5 times a day for 15 minutes in every 15 minutes for 10 days. After completing intermittent hypoxic training, in acute experiments on anesthetized with urethane (1700 mg/kg) rats, we studied changes in the SAP induced by a modulation of neuronal NO-synthase (NOS-1) activity in the neurons of the medullary cardiovascular nuclei (nucleus of tractus solitarius, NTS; nucleus ambiguous, AMB, lateral reticular nucleus, (LRN). In control rats housed in normoxic conditions, NOS-1 activation with injections of L-arginine (5.8 − 58 nM) into the medullary nuclei involved in the cardiovascular control induced the SAP lowering in most experiments in a dose-dependent manner. In rats submitted to intermittent hypoxic training, NOS-1 activation with injections of L-arginine (5.8 − 58 nM) into the medullary nuclei under study resulted in hypotensive responses which were more expressed as compared with those responses induced by its injections into the medullary nuclei in rats under normoxia. The data obtained give evidence for some additional activation of neuronal NO-synthase in the neurons of the medullary nuclei following intermittent hypoxic training. Effects of NOS-1 activation were comparable in all the tested nuclei. An effect of NOS-1 activation was quite short-lasting; it was the most pronounced on the first day after completing hypoxic training. In three days after hypoxic training, injections of L-arginine into tested medullary nuclei resulted in the SAP drop that was similar to that in control animals housed in normoxic conditions. On the contrary, inhibition of NOS-1 in the neurons induced by injections of NOS-1-antagonist L-NNA (23 nM) into the medullary cardiovascular nuclei resulted in a comparable increase in the SAP in both control and hypoxically trained rats. Effects of L-arginine injections into the medullary nuclei were blocked by preliminary administrating of a specific NOS-1 inhibitor 7-nitroindazol. On the first day after intermittent hypoxic training we observed the SAP elevation. Although it was statistically insignificant, and we observed the elevated SAP just after completing hypoxic training, these data provide evidence to support the concept that rats submitted to intermittent hypoxia exhibit an increase in sympathetic activity. The SAP elevation might be also induced by the stressor effect of keeping rats in a chamber to provide hypoxic training. There is an impression that intermittent hypoxic training might lead to two simultaneous but opposite directed results: an activation of sympathetic nervous system and an activation of NOS-1 in the medullary neurons.
Neutrophil Apoptosis and Hypoxia
389-400
10.1615/IntJPhysPathophys.v1.i4.90
Andrey
Polyakov
Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Larissa
Dyugovskaya
Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
neutrophils
apoptosis
hypoxia
Neutrophils are the most abundant population of leukocytes, which constitute the defense against pathogens. Released by neutrophils the proteolytic enzymes and reactive oxygen species help in eliminating infections, but also cause extensive tissue damage. Neutrophil apoptosis plays an essential role in cell homeostasis and resolution of inflammation. It is mediated by a complex network of intracellular apoptotic/survival signaling pathways and can be modulated by a variety of extracellular stimuli such as hypoxia. Here, we review recent studies on the mechanisms of neutrophil death and survival accentuating on neutrophil apoptosis under hypoxic conditions. Neutrophils possess components of both extrinsic and intrinsic apoptotic routes. However, in neutrophils this mechanism has special features. The involvement of death receptors, caspases, mitochondria, and Bcl-2 proteins are discussed. Both the transcription factor NF-κB and p38MAPK regulate the neutrophil apoptotic program. Despite that reactive oxygen species (ROS) can directly promote and/or adjust apoptosis, there is no consensus about the role of ROS on neutrophil lifespan. Thus both the types of ROS involved and the site of their generation may be important for neutrophil apoptosis. Finally, hypoxia can activate several signaling pathways. The possible differences between the effects of sustained and intermittent hypoxia are also addressed.