I. Byelinska, O. Lynchak, S. M. Tsyvinska, V. Rybalchenko
The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug
{"title":"[MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].","authors":"I. Byelinska, O. Lynchak, S. M. Tsyvinska, V. Rybalchenko","doi":"10.15407/FZ61.04.071","DOIUrl":"https://doi.org/10.15407/FZ61.04.071","url":null,"abstract":"The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"17 1","pages":"71-7"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87288636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Brechka, V. Nevzorov, V. Bondarenko, N. Malova, N. Selyukova
The results of study of ultrastructural changes in the Sertoli cells and Leydig's cells organelles after destructive influence of the serotonin hydrochloride and under influence bioglobin-U have been presented. It was shown that serotonin hydrochloride causes mitochondrial dysfunction and activates intracellular catabolic processes on the intracellular level. Bioglobin-U increases the activity and reparative synthetic reactions, reduced the degree of mitochondrial dysfunction and catabolic processes and activate the Leydig cell metabolism, and significantly reduces the number of foci destruction membranes of the endoplasmic reticulum, mitochondrial, and membranes of nucleus on the background of serotonin hydrochloride.
{"title":"[INVESTIGATIONS OF SUBMICROSCOPIC ARCHITECTONICS SERTOLI AND LEYDIG CELLS AFTER HYDROCHLORIDE SEROTONIN DESTRUCTIVE IMPACT AND THE POSSIBILITY OF CORRECTION BY STIMULANTS OF METABOLIC PROCESSES].","authors":"N. Brechka, V. Nevzorov, V. Bondarenko, N. Malova, N. Selyukova","doi":"10.15407/FZ61.04.085","DOIUrl":"https://doi.org/10.15407/FZ61.04.085","url":null,"abstract":"The results of study of ultrastructural changes in the Sertoli cells and Leydig's cells organelles after destructive influence of the serotonin hydrochloride and under influence bioglobin-U have been presented. It was shown that serotonin hydrochloride causes mitochondrial dysfunction and activates intracellular catabolic processes on the intracellular level. Bioglobin-U increases the activity and reparative synthetic reactions, reduced the degree of mitochondrial dysfunction and catabolic processes and activate the Leydig cell metabolism, and significantly reduces the number of foci destruction membranes of the endoplasmic reticulum, mitochondrial, and membranes of nucleus on the background of serotonin hydrochloride.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"24 1","pages":"85-91"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87469391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We studied the spontaneous and metal induced oxidation of lipids and proteins in in vitro modeling ways of lipid peroxidation and blood proteins in the formation of malondialdehyde (MDA) and protein carbonyl groups (PCG) in 86 patients with chronic pyelonephritis (cPN) and 64 patients chronic glomerulonephritis(cGN) without prejudice excretory function of the kidneys. Installed the increase in the blood of patients with cPN MDAs 2 times, MDAe--14%, PCG 1.5 times; and cGN--MDAs 2.3 times, MDAe--29%, PCG--2 times. Found increased MDA content and PCG in the blood of patients with cPN and more expressive when cGN. Stimulation of in vitro peroxidation processes contributed significantly increased of production of MDA comparedwith baseline. In the modeling in vitro ascorbate-dependent and NADPH-dependent lipid peroxidation ways and the increase in protein production of MDA and PCG in both groups of patients, especially in the NADPH-dependent way, which must be considered in the correction of oxidative processes and antioxidant therapy appointment.
{"title":"[MODELING IN VITRO PATHWAYS OF ACTIVATION OF LIPID PEROXIDATION AND PROTEIN IN CHRONIC KIDNEY DISEASE].","authors":"L. Korol","doi":"10.15407/FZ61.04.092","DOIUrl":"https://doi.org/10.15407/FZ61.04.092","url":null,"abstract":"We studied the spontaneous and metal induced oxidation of lipids and proteins in in vitro modeling ways of lipid peroxidation and blood proteins in the formation of malondialdehyde (MDA) and protein carbonyl groups (PCG) in 86 patients with chronic pyelonephritis (cPN) and 64 patients chronic glomerulonephritis(cGN) without prejudice excretory function of the kidneys. Installed the increase in the blood of patients with cPN MDAs 2 times, MDAe--14%, PCG 1.5 times; and cGN--MDAs 2.3 times, MDAe--29%, PCG--2 times. Found increased MDA content and PCG in the blood of patients with cPN and more expressive when cGN. Stimulation of in vitro peroxidation processes contributed significantly increased of production of MDA comparedwith baseline. In the modeling in vitro ascorbate-dependent and NADPH-dependent lipid peroxidation ways and the increase in protein production of MDA and PCG in both groups of patients, especially in the NADPH-dependent way, which must be considered in the correction of oxidative processes and antioxidant therapy appointment.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"53 1","pages":"92-7"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91328949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/INTJPHYSPATHOPHYS.V7.I2.60
V. Berezovskyĭ, I. G. Litovka, S. Veselskyi, R. Janko, U. A. Zhernoklev
It was investigated in spring 28-day experiment the administration of pharmacological doses (5 mg/kg) of melatonin to 3-month male rats with high and low levels of energy metabolismat remodeling of bone tissue. It was shown the decrease in activity of osteoblast and increase of osteoclast activity regardless of energy metabolism intensity, increase in concentration of glycosaminoglycans and free amino acids. This indicates the inhibition of physiological bone remodeling and helps to maintain the integrity of the organic matrix and the inorganic component of the fixation of the connective tissue - hydroxyapatite crystals.
{"title":"[THE EFFECT OF EXOGENOUS MELATONIN ON BONE REMODELING].","authors":"V. Berezovskyĭ, I. G. Litovka, S. Veselskyi, R. Janko, U. A. Zhernoklev","doi":"10.1615/INTJPHYSPATHOPHYS.V7.I2.60","DOIUrl":"https://doi.org/10.1615/INTJPHYSPATHOPHYS.V7.I2.60","url":null,"abstract":"It was investigated in spring 28-day experiment the administration of pharmacological doses (5 mg/kg) of melatonin to 3-month male rats with high and low levels of energy metabolismat remodeling of bone tissue. It was shown the decrease in activity of osteoblast and increase of osteoclast activity regardless of energy metabolism intensity, increase in concentration of glycosaminoglycans and free amino acids. This indicates the inhibition of physiological bone remodeling and helps to maintain the integrity of the organic matrix and the inorganic component of the fixation of the connective tissue - hydroxyapatite crystals.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"os-19 1","pages":"64-9"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87200991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/INTJPHYSPATHOPHYS.V7.I3.50
A. Reznikov, N. Nosenko, L. Tarasenko, A. Limareva
The changes of aromatase and 5α-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3-month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress.
{"title":"[CHANGES IN THE BRAIN TESTOSTERONE METABOLISM AND SEXUAL BEHAVIOR IN MALE RATS PRENATALLY EXPOSED TO METHYLDOPA AND STRESS].","authors":"A. Reznikov, N. Nosenko, L. Tarasenko, A. Limareva","doi":"10.1615/INTJPHYSPATHOPHYS.V7.I3.50","DOIUrl":"https://doi.org/10.1615/INTJPHYSPATHOPHYS.V7.I3.50","url":null,"abstract":"The changes of aromatase and 5α-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3-month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"165 1","pages":"41-7"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74114233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Dorofeyeva, A. Kotsuruba, B. S. Kopjak, V. Sagach
In the heart and heart mitochondria spontaneously hypertensive rats investigated the effect of physical exercise training (swimming in a moderate and excessive training mode) on the physiological indicators of cardiac hemodynamics and biochemical parameters that characterize the level of oxidative and nitrosative stress. The index of coupling Ca(2+)-dependent constitutive NO-synthases (cNOS = eNOS + nNOS) and biochemical index of dysfunction were calculated. It turned out that both modes of training is completely restored, and even exceed the reference values in untrained rats Wistar conjugate cNOS state and Ca(2+)-dependent synthesis of nitric oxide (NO). Intensity regime of exercise on the border of functionality have been ineffective for improving the functional state of the cardiovascular system and hypertension can provoke it further. Moderate physical training regime, on the contrary, improves the diastolic function of the heart due to an increase dP/dtmin, reducing end-diastolic pressure and a significant reduction in end-diastolic stiffness. Moderate exercise decreased peripheral resistance and cardiac afterload, as indicated by the decrease in end-systolic pressure and arterial stiffness, which contributed to more efficient and energy-saving of heart work. Improve physiological indicators of cardiac hemodynamics and functional state of the heart in moderate mode of training correlated with changes in both the calculated indices. Moderate mode of training is recommended as a simple physiological preconditioning method for the prevention of cardiac dysfunction, hypertension as a result of state uncoupling cNOS and the resulting excessive generation of superoxide and, conversely, inhibition of Ca(2+)-dependent synthesis of NO.
{"title":"[PHYSICAL EXERCISE TRAINING CAN- CELS CONSTITUTIVE NOS UNCOUPLING AND INDUCED VIOLATIONS OF CARDIAC HEMODYNAMICS IN HYPERTENSION (PART III)].","authors":"N. Dorofeyeva, A. Kotsuruba, B. S. Kopjak, V. Sagach","doi":"10.15407/FZ61.04.011","DOIUrl":"https://doi.org/10.15407/FZ61.04.011","url":null,"abstract":"In the heart and heart mitochondria spontaneously hypertensive rats investigated the effect of physical exercise training (swimming in a moderate and excessive training mode) on the physiological indicators of cardiac hemodynamics and biochemical parameters that characterize the level of oxidative and nitrosative stress. The index of coupling Ca(2+)-dependent constitutive NO-synthases (cNOS = eNOS + nNOS) and biochemical index of dysfunction were calculated. It turned out that both modes of training is completely restored, and even exceed the reference values in untrained rats Wistar conjugate cNOS state and Ca(2+)-dependent synthesis of nitric oxide (NO). Intensity regime of exercise on the border of functionality have been ineffective for improving the functional state of the cardiovascular system and hypertension can provoke it further. Moderate physical training regime, on the contrary, improves the diastolic function of the heart due to an increase dP/dtmin, reducing end-diastolic pressure and a significant reduction in end-diastolic stiffness. Moderate exercise decreased peripheral resistance and cardiac afterload, as indicated by the decrease in end-systolic pressure and arterial stiffness, which contributed to more efficient and energy-saving of heart work. Improve physiological indicators of cardiac hemodynamics and functional state of the heart in moderate mode of training correlated with changes in both the calculated indices. Moderate mode of training is recommended as a simple physiological preconditioning method for the prevention of cardiac dysfunction, hypertension as a result of state uncoupling cNOS and the resulting excessive generation of superoxide and, conversely, inhibition of Ca(2+)-dependent synthesis of NO.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"100 1","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87020898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The paper presents the results of research, allowing to establish the need for and feasibility of an integrated method to determine the most effective but at the same time safe modes of load to the body troops. We found that despite the rather promising application of our proposed mode of load of high intensity (Ra = 0.71) to increase the level of physical military training as soon as possible in time of peace (with a minimum set of combat equipment), problematic issue is that in most cases there is a complete-mismatch achieved in the degree of physical development of the body of military requirements and the challenges posed in terms of direct hostilities. Using the integral method developed by us we determine the safest modes of exercise for the military servants to optimize the most appropriate parameters of volume and intensity of the load, and speed up the adaptive changes in their body to enhance maximum performance at this stage of preparation.
{"title":"[DETERMINATION OF THE OPTIMAL SAFE MODE OF PHYSICAL ACTIVITY FOR THE MILITARY SERVANTS UNDER CONDITIONS CLOSE TO FIGHTING].","authors":"A. Chernozub, Y. Radchenko","doi":"10.15407/FZ61.06.069","DOIUrl":"https://doi.org/10.15407/FZ61.06.069","url":null,"abstract":"The paper presents the results of research, allowing to establish the need for and feasibility of an integrated method to determine the most effective but at the same time safe modes of load to the body troops. We found that despite the rather promising application of our proposed mode of load of high intensity (Ra = 0.71) to increase the level of physical military training as soon as possible in time of peace (with a minimum set of combat equipment), problematic issue is that in most cases there is a complete-mismatch achieved in the degree of physical development of the body of military requirements and the challenges posed in terms of direct hostilities. Using the integral method developed by us we determine the safest modes of exercise for the military servants to optimize the most appropriate parameters of volume and intensity of the load, and speed up the adaptive changes in their body to enhance maximum performance at this stage of preparation.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"76 1","pages":"69-75"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79148079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Drachuk, N. Dorofeyeva, A. Kotsjuruba, V. Sagach
Aging increases the risk of cardiovascular diseases. The objective of this study was to show the effect of propargylg- lycine (PPG) upon cardiohemodynamics in old rats. We used pressure-volume (PV) conductance catheter system (Millar Instruments, USA) in order to evaluate systolic and diastolic function in vivo. It has been shown that introducted PPG (11,31 mg/kg) decrises both arterial stiffness (by 1,5 times) and end-diastolic stiffness (by 2,1 times) in old rats. Using PPG in heart mitochondria resulted in increasing levels of H2S (by 112%), NO2- (by 162%) and in growing activity of cNOS (by 3 times). Additionally, PPG decreased the mitochondrial pools of the uric acid, the marker of the superoxide (*O2-) formation and of the ATP degradation. These results suggest that PPG activates alternative ways of H2S synthesis, stimulates the NO and H2S synthesis and suppresses the ATP degradation and *O2 formation. These actions of PPG improve arterial stiffness and end-diastolic stiffness.
{"title":"[EFFECT OF PROPARGYLGLYCINE UPON CARDIOHEMODYNAMICS IN OLD RATS].","authors":"K. Drachuk, N. Dorofeyeva, A. Kotsjuruba, V. Sagach","doi":"10.15407/FZ61.04.035","DOIUrl":"https://doi.org/10.15407/FZ61.04.035","url":null,"abstract":"Aging increases the risk of cardiovascular diseases. The objective of this study was to show the effect of propargylg- lycine (PPG) upon cardiohemodynamics in old rats. We used pressure-volume (PV) conductance catheter system (Millar Instruments, USA) in order to evaluate systolic and diastolic function in vivo. It has been shown that introducted PPG (11,31 mg/kg) decrises both arterial stiffness (by 1,5 times) and end-diastolic stiffness (by 2,1 times) in old rats. Using PPG in heart mitochondria resulted in increasing levels of H2S (by 112%), NO2- (by 162%) and in growing activity of cNOS (by 3 times). Additionally, PPG decreased the mitochondrial pools of the uric acid, the marker of the superoxide (*O2-) formation and of the ATP degradation. These results suggest that PPG activates alternative ways of H2S synthesis, stimulates the NO and H2S synthesis and suppresses the ATP degradation and *O2 formation. These actions of PPG improve arterial stiffness and end-diastolic stiffness.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"4 1","pages":"35-40"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78612430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Tykhomyrov, D. Zhernosekov, Y. M. Roka-Moya, S. I. Diordieva, T. Grinenko
The effects of Lys-plasminoge on platelet α-granule secretion were studied. The level of P-selectin exposed on the surface of plasma membranes of washed human platelets was measured by flow cytometry as a market of α-granule secretion. It was shown that Lys-plasminogen facilitates partial release of α-granules, but impedes thrombin-induced platelet exocytosis. It is suggested that Lys-plasminogen may affect platelet secretion rather through interaction of its non-catalytic (kringle) domains with membrane receptors than due to contaminating plasmin activity. In contrast to Lys-form, native proenzyme (Glu-plasminogen) had no effects on α-granule releasing. Here, we provide the first experimental demonstration that Lys-form of plasminogen is able to modulate platelet α-granule secretion, and this effect can be considered as one of the plausible mechanisms of its anti-aggregating activity.
{"title":"[THE EFFECTS OF LYS-PLASMINOGEN ON HUMAN PLATELET SECRETION].","authors":"A. Tykhomyrov, D. Zhernosekov, Y. M. Roka-Moya, S. I. Diordieva, T. Grinenko","doi":"10.15407/FZ61.06.026","DOIUrl":"https://doi.org/10.15407/FZ61.06.026","url":null,"abstract":"The effects of Lys-plasminoge on platelet α-granule secretion were studied. The level of P-selectin exposed on the surface of plasma membranes of washed human platelets was measured by flow cytometry as a market of α-granule secretion. It was shown that Lys-plasminogen facilitates partial release of α-granules, but impedes thrombin-induced platelet exocytosis. It is suggested that Lys-plasminogen may affect platelet secretion rather through interaction of its non-catalytic (kringle) domains with membrane receptors than due to contaminating plasmin activity. In contrast to Lys-form, native proenzyme (Glu-plasminogen) had no effects on α-granule releasing. Here, we provide the first experimental demonstration that Lys-form of plasminogen is able to modulate platelet α-granule secretion, and this effect can be considered as one of the plausible mechanisms of its anti-aggregating activity.","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"62 1","pages":"26-34"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80667940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Kulyk, I. Chizhmakov, T. M. Volkova, O. Maximyuk, O. Krishtal
Homomeric P2X3 receptors expressed in primary nociceptive neurons are crucial elements in the pain signal generation. In turn, opioid system regulates the intensity of this signal in both CNS and PNS. Here we describe the effects of opioids on P2X3 receptors in DRG neurons studied by using patch clamp technique. Activation of G-protein coupled opioid receptors by endogenous opioid Leu-enkephalin (Leu), resulted in the two opposite effects on P2X3 receptor-mediated currents (P2X3 currents). In particular, application of 1 µM Leu lead to the complete inhibition of P2X3 currents. However, after pretreatment of the neurons with a Gi/o-protein inhibitor pertussis toxin (PT), the same concentration of Leu caused facilitation of P2X3 currents. PLC inhibitor U-73122 at concentration of 1 µM completely eliminated both facilitating and inhibitory effects of Leu on P2X3 currents. Thus, opioid receptor agonists cause two oppositely directed effects on P2X3 receptors in DRG neurons of rats and both of them are mediated through PLC signaling pathway. Our results point to a possible molecular basis of the mechanism for the well-known transition inhibitory action of opioids (analgesia) to facilitating (hyperalgesia).
{"title":"[ROLE PHOSPHOINOSITID SIGNALING PATHWAY IN OPIOIDS CONTROL OF P2X3 RECEPTORS IN THE PRIMARY SENSORY NEURONS].","authors":"V. Kulyk, I. Chizhmakov, T. M. Volkova, O. Maximyuk, O. Krishtal","doi":"10.15407/FZ61.04.022","DOIUrl":"https://doi.org/10.15407/FZ61.04.022","url":null,"abstract":"Homomeric P2X3 receptors expressed in primary nociceptive neurons are crucial elements in the pain signal generation. In turn, opioid system regulates the intensity of this signal in both CNS and PNS. Here we describe the effects of opioids on P2X3 receptors in DRG neurons studied by using patch clamp technique. Activation of G-protein coupled opioid receptors by endogenous opioid Leu-enkephalin (Leu), resulted in the two opposite effects on P2X3 receptor-mediated currents (P2X3 currents). In particular, application of 1 µM Leu lead to the complete inhibition of P2X3 currents. However, after pretreatment of the neurons with a Gi/o-protein inhibitor pertussis toxin (PT), the same concentration of Leu caused facilitation of P2X3 currents. PLC inhibitor U-73122 at concentration of 1 µM completely eliminated both facilitating and inhibitory effects of Leu on P2X3 currents. Thus, opioid receptor agonists cause two oppositely directed effects on P2X3 receptors in DRG neurons of rats and both of them are mediated through PLC signaling pathway. Our results point to a possible molecular basis of the mechanism for the well-known transition inhibitory action of opioids (analgesia) to facilitating (hyperalgesia).","PeriodicalId":12306,"journal":{"name":"Fiziolohichnyi zhurnal","volume":"130 1","pages":"22-9"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79610739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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