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1.
Bull Exp Biol Med ; 164(3): 298-303, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29308570

RESUMEN

Hypoxia-induced immediate expression of transcription factor HIF-1α in the brain cortex is regulated by succinate produced in both the tricarbonic acid cycle and GABA shunt reactions and is induced by succinate-containing drugs. These facts prove the existence of succinate-dependent signalling regulation involved in immediate and delayed molecular adaptation and increased body resistance to oxygen deficiency, where succinate acts as a signal molecule. The intensity of this process differs in animals with low and high resistance to hypoxia.


Asunto(s)
Adaptación Fisiológica , Mal de Altura/genética , Corteza Cerebral/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Succinato Deshidrogenasa/genética , Ácido Succínico/metabolismo , Mal de Altura/metabolismo , Mal de Altura/fisiopatología , Animales , Corteza Cerebral/efectos de los fármacos , Ciclo del Ácido Cítrico/efectos de los fármacos , Ciclo del Ácido Cítrico/genética , Modelos Animales de Enfermedad , Complejo I de Transporte de Electrón/antagonistas & inhibidores , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo II de Transporte de Electrones/antagonistas & inhibidores , Complejo II de Transporte de Electrones/genética , Complejo II de Transporte de Electrones/metabolismo , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Fenobarbital/farmacología , Picolinas/farmacología , Ratas , Ratas Endogámicas , Semicarbacidas/farmacología , Transducción de Señal , Succinato Deshidrogenasa/metabolismo , Ácido Succínico/farmacología , Ácido gamma-Aminobutírico/metabolismo
2.
Bull Exp Biol Med ; 160(6): 742-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27165084

RESUMEN

Under normoxic conditions, succinate-dependent receptor GPR91 was found in varying amounts in all analyzed aerobic tissues except erythrocytes. The maximum density of the receptor was observed in the myocardium: by 2.3 and 1.7 times higher than in the kidneys and brain cortex, respectively. Hypoxic expression of GPR91 was tissue-specific, depended on the duration and severity of hypoxia, and did not correlate with the basal level of this receptor. It was maximum in the brain cortex, which confirms the high importance of this signal pathway for brain functioning. Single hypoxic exposure induced immediate expression of GPR91 in the brain cortex within 15-60 min, which correlated with the development of urgent tolerance to hypoxia of the body. Induction of immediate expression of GPR91 in brain cortex occurred during first 15-60 min and correlated to the forming of immediate tolerance of organism to hypoxia. Brain cortex-specific immediate expression of GPR91 during hypoxia was related to activity of the GABA-bypass that acts as the source of succinate for the receptor under these conditions.


Asunto(s)
Expresión Génica , Receptores Acoplados a Proteínas G/metabolismo , Animales , Hipoxia de la Célula , Corteza Cerebral/metabolismo , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Especificidad de Órganos , Ratas , Receptores Acoplados a Proteínas G/genética , Ácido Succínico/metabolismo , Activación Transcripcional
3.
Patol Fiziol Eksp Ter ; (3): 9-16, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-25536785

RESUMEN

Using immunohistochemical method, it was demonstrated that neurons of the cerebral cortex have the capacity to express hypoxia-inducible factor-1 alpha (HIF-1α) in normoxia. Intensity of this process is different for rats having unequal tolerance to hypoxia. Basal HIF-1α expression in neurons of rats with low-resistance (LR) to hypoxia is higher compared to rats with high-resistance (HR). Bilateral photochemically induced focal ischemic insult in the rat prefrontal cortex completely suppressed HIF-1α neuronal expression the in the ischemic zone and only partially--in the area of the penumbra. Neuronal injury was more pronounced in cortex of LR rats compared to HR rats. These findings suggest that functional significance of HIF-1α is greater in neurons of the cerebral cortex of LR rats compared to HR rats.


Asunto(s)
Isquemia Encefálica/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/metabolismo , Neocórtex/metabolismo , Corteza Prefrontal/metabolismo , Accidente Cerebrovascular/metabolismo , Animales , Hipoxia/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neocórtex/patología , Neuronas/metabolismo , Especificidad de Órganos , Corteza Prefrontal/patología , Ratas
4.
Patol Fiziol Eksp Ter ; (4): 30-9, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-25980224

RESUMEN

Clinical and epidemiological data evidence the need to search for new substances for treatment and prevention of increased anxiety associated with emotional and neurotic breakdown and worsening clinical prognosis of psychosomatic diseases. Of particular interest are the drugs of plant origin, which are generally well tolerated under prolonged use, and treat- ment is cheaper as compared with modem anxiolytics. The purpose of this study was to investigate the effects of course taking a flavonoid-containing plant preparation Extralife (water-soluble extract Pentaphylloides fruticosa, 40 mg/kg per day for 1 month) in <> and <> inbred albino rats sampled in the population using a multi-parameter method for evaluating anxiety-phobic states. This method was also used for evaluating the severity of anxiety (state anxiety) in rats in the dynamics of the survey. Sensorimotor reactivity (emotionality) was assessed by the parameters of the acoustic startle response. Extralife did not prevent the increase in state anxiety in <> rats and did not change the level of anxiety in the <> animals. However, the drug reduced the amplitude of the acoustic startle response in the <> animals and increased startle response latency in both <> and <> rats, that is reduced the symptoms of anxiety caused by alarm sound stimuli in terms of sensorimotor reactivity. The data testify to the anxiolytic and sedative effects of Extralife more pronounced in the <> animals. In a course intake of Extralife <> rats demonstrated transient decrease in the pre-pulse inhibition of the acoustic startle response, probably associated with the occurrence of transient disturbances in the psycho-emotional sphere. The findings suggest that Extralife in a course taking may have negative side effects on the emotionality of animals that determines the need to incorporate the features of mental and emotional status of the individual in the development of therapeutic approaches to the correction of high anxiety with the inclusion of the drug.


Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Emociones/efectos de los fármacos , Retroalimentación Sensorial/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Estimulación Acústica , Adaptación Psicológica , Animales , Trastornos de Ansiedad/fisiopatología , Trastornos de Ansiedad/psicología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Actividad Motora/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Ratas , Reflejo de Sobresalto/efectos de los fármacos , Reflejo de Sobresalto/fisiología
5.
Bull Exp Biol Med ; 154(5): 597-601, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23658877

RESUMEN

The development of immediate and delayed long-term resistance to hypoxia during a course of intermittent normobaric hypoxia (15 daily sessions of alternating exposure to 10% O2 and atmospheric air for 1 h) correlated with biphasic expression of HIF-1α in neocortex of hypoxia-intolerant rats, which suggests involvement of this protein factor not only in the formation of long-term adaptation, but also in triggering immediate adaptation to hypoxia. Both processes develop under conditions promoting down-regulation of oxidative modification of LDL and increasing tolerance of biological membranes to hypoxia in the absence of activation of the free radical processes, which therefore do not trigger HIF-1α expression under these conditions. Neither cytokines nor NO are the inducers of immediate adaptation, and they are not related to HIF-1α expression during the early post-hypoxic period. In contrast, long-term adaptation in response to the course of intermittent normobaric hypoxia develops against the background of enhanced NO production, activation of pro- and anti-inflammatory factors, and expression of VEGF, the marker of angiogenesis. Therefore, all these factors can promote activation of transcription processes required to form the long-term adaptation.


Asunto(s)
Adaptación Fisiológica , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Hipoxia/metabolismo , Metabolismo de los Lípidos , Óxido Nítrico/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Animales , Hipoxia de la Célula , Citocinas/sangre , Hipoxia/sangre , Lipoproteínas LDL/biosíntesis , Lipoproteínas LDL/sangre , Neovascularización Fisiológica , Óxido Nítrico/biosíntesis , Ratas , Factor A de Crecimiento Endotelial Vascular/biosíntesis
6.
Bull Exp Biol Med ; 154(6): 718-22, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23658906

RESUMEN

There are tissue-specific and phenotypic differences in the basal levels of HIF-1α under normoxic conditions. Induction of short-term adaptation to hypoxia and formation of long-term adaptation are genetically determined. These phenomena are observed only in animals with low resistance to hypoxia and are associated with biphasic expression of HIF-1α in the neocortex only during hypoxic preconditioning. Severe hypoxia disorders HIF-1α expression and impairs the formation of short-term and long-term resistance. In animals with high resistance to hypoxia, neither short-term nor long-term resistance develops in response to hypoxic exposure, and this correlates with the absence of changes in post-hypoxic HIF-1α levels in the neocortex.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neocórtex/metabolismo , Adaptación Fisiológica , Animales , Animales no Consanguíneos , Hipoxia de la Célula , Regulación de la Expresión Génica , Masculino , Especificidad de Órganos , Fenotipo , Ratas
7.
Bull Exp Biol Med ; 151(1): 25-9, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-22442795

RESUMEN

Activity of mitochondrial ATP-dependent potassium channel in rats with high genetically determined resistance to hypoxia was higher than in sensitive animals. Adaptation of low resistant rats to hypoxia was accompanied by activation of the channel, facilitation of potassium recycling in mitochondria, and a decrease in the rate of H2O2 formation. Our results indicate that mitochondrial ATP-dependent potassium channel plays an important role in the delayed mechanisms of animal's adaptation to hypoxia.


Asunto(s)
Aclimatación/fisiología , Hipoxia/metabolismo , Canales KATP/metabolismo , Potasio/metabolismo , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Animales , Resistencia a la Enfermedad , Peróxido de Hidrógeno/metabolismo , Hipoxia/genética , Hipoxia/fisiopatología , Canales KATP/agonistas , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Ratas
8.
Bull Exp Biol Med ; 151(3): 292-6, 2011 Jul.
Artículo en Inglés, Ruso | MEDLINE | ID: mdl-22451869

RESUMEN

We studied the effect of single hypoxic preconditioning exposure (hypobaric hypoxia, 5000 m, 60 min) on free radical processes, glutathione system, and antioxidant defense enzymes in tissues of rats with different resistance to acute hypoxia. The intensity of free radical processes was shown to increase or decrease on day 1 after hypoxic preconditioning. These changes were tissue-specific and opposite in animals with genetically determined differences in the resistance to hypoxia. Hypoxic preconditioning contributes to the immediate resistance. The effect was more pronounced in low resistant animals, who did not exhibit signs of oxidative stress in tissues during the early posthypoxic period. By contrast, hypoxic preconditioning was followed by activation of free radical processes in tissues of highly resistant animals. These rats were characterized by low ability for the development of immediate resistance. Activation of free radical processes in the early period of adaptation (first hours after hypoxic preconditioning) does not play a role in the induction of immediate adaptive mechanisms for hypoxia.


Asunto(s)
Antioxidantes/metabolismo , Radicales Libres/metabolismo , Glutatión/metabolismo , Hipoxia/metabolismo , Precondicionamiento Isquémico , Animales , Masculino , Estrés Oxidativo , Oxígeno , Ratas
9.
Bull Exp Biol Med ; 150(6): 685-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22235417

RESUMEN

Different modes of hypoxic exposure led to phasic changes in activities of the complement system components in rats sensitive to hypoxia starting from the first minutes of the posthypoxic period and persisting for 24 h and longer. The direction of shifts in the complement system depended on the duration and intensity of oxygen deficiency. Single one-hour interval hypoxia led to a moderate elevation of activities of virtually all the studied components. A more intense hypoxic exposure (1-h hypobaric hypoxia at a height of 5000 m) induced a biphasic response: reduction of activities of the majority of complement system components during the first hour of posthypoxic period and subsequent elevation of these activities above the normal. Exposure to severe hypobaric hypoxia (7000 m) led to a longer and more pronounced primary reduction of complement components activities, while the phase of their activity increase was blurred. Animal capacity to the formation of urgent tolerance of hypoxia was retained and increased with increasing the severity of hypoxic exposure. The complement consumption during the posthypoxic period was presumably a programmed reaction preventing hyperactivation of complement system components and essential for tolerance formation.


Asunto(s)
Proteínas del Sistema Complemento/metabolismo , Hipoxia/sangre , Animales , Oxígeno , Ratas
10.
Bull Exp Biol Med ; 147(4): 400-4, 2009 Apr.
Artículo en Inglés, Ruso | MEDLINE | ID: mdl-19704933

RESUMEN

Single exposure to moderate (10% O(2)) hypobaric, normobaric, and intermittent hypoxia is followed by a preconditioning response of the organism. The mechanisms for immediate adaptation are activated during the hypoxic period. Intermittent reoxygenation not only delays, but even suppresses this process. However, periods of oxygenation during the course of hypoxic training reduce the effect of hypoxia and prevent the possibility for "overdosage" of the adverse stimulus. Hence, they have a regulatory or normalizing role under these conditions. Our results indicate that hypoxitherapy in intermittent hypoxia mode provides optimum conditions for long-term adaptation.


Asunto(s)
Hipoxia/prevención & control , Hipoxia/fisiopatología , Oxígeno/metabolismo , Animales , Frecuencia Cardíaca/fisiología , Masculino , Distribución Aleatoria , Ratas , Factores de Tiempo
11.
Bull Exp Biol Med ; 148(4): 587-91, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20396747

RESUMEN

Succinate-containing derivatives of 3-hydroxypyridine, mexidol and proxypin, serve as succinate donors for the respiratory chain and contribute to activation of the succinate oxidase pathway of oxidation. Under conditions of hypoxia, these changes promote recovery of aerobic energy production, normalization of intracellular ATP concentration, and development of the antihypoxic effect. Succinate-free analogues of the test compounds exhibit no such properties. Both agents are considered as energotropic substances. The specific effect of these compounds is manifested in direct interaction with the respiratory chain and normalization of ATP synthesis under conditions of hypoxia/ischemia. The test compounds can be used for the correction of energy metabolism disorders during acute oxygen deficiency. Moreover, they can be used for the treatment of associated functional disturbances.


Asunto(s)
Antioxidantes , Transporte de Electrón/efectos de los fármacos , Picolinas , Piridinas , Succinatos , Adenosina Trifosfato/metabolismo , Amobarbital/farmacología , Animales , Antioxidantes/química , Antioxidantes/farmacología , Transporte de Electrón/fisiología , Metabolismo Energético/efectos de los fármacos , Hipnóticos y Sedantes/farmacología , Malonatos/farmacología , Oxidación-Reducción , Fosfocreatina/metabolismo , Picolinas/química , Picolinas/farmacología , Piridinas/química , Piridinas/farmacología , Ratas , Succinatos/química , Succinatos/farmacología
12.
Bull Exp Biol Med ; 146(2): 229-33, 2008 Aug.
Artículo en Inglés, Ruso | MEDLINE | ID: mdl-19145325

RESUMEN

Flavonoid-containing plant preparations (water soluble extracts of Pentaphylloides fruticosa [Extralife], Emblica officinalis Gaerth [Amla], and Bergenia crassifolia [Bergenia]) produced a dose-dependent and tissue-specific effect on activity of mitochondrial ATP-dependent potassium channel. The effect of these preparations was biphasic (activation and inhibition). The activating effect of Extralife was one order of magnitude higher than that of Amla and Bergenia and was observed in a wider concentration range. The activating effect of preparations was abolished by inhibitors of the mitochondrial ATP-dependent potassium channel, which attested to specificity of their influence on mitochondrial channel. Under in vivo conditions, the antihypoxic effect of Extralife was partially abolished by mitochondrial ATP-dependent potassium channel inhibitor 5-hydroxydecanoate.


Asunto(s)
Flavonoides/farmacología , Canales KATP/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Hipoxia de la Célula , Ácidos Decanoicos/farmacología , Relación Dosis-Respuesta a Droga , Hidroxiácidos/farmacología , Canales KATP/antagonistas & inhibidores , Mitocondrias Cardíacas/metabolismo , Mitocondrias Hepáticas/metabolismo , Dilatación Mitocondrial/efectos de los fármacos , Phyllanthus emblica , Postura , Ratas
13.
Bull Exp Biol Med ; 144(6): 795-801, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18856204

RESUMEN

We studied the effect of intermittent normobaric hypoxia on the formation of adaptive signs and state of mitochondrial enzymes in the cerebral cortex of rats with different resistance to hypoxia. Kinetic parameters for mitochondrial enzymes in the substrate region of the respiratory chain of the cerebral cortex underwent various changes in low resistant and highly resistant rats over the first 2 h after 1-h intermittent normobaric hypoxia. Low resistant animals were characterized by more effective functioning of rotenone-sensitive NADH-cytochrome C reductase and succinate-cytochrome C reductase under conditions of increased reduction status of the cell. These features correlated with the increase in the general resistance of animals. Significant changes in kinetic properties of mitochondrial enzymes and signs of the development of resistance were not found in highly resistant rats. Reciprocal relations between mitochondrial enzyme complexes in the substrate region of the respiratory chain probably play a role of the signal regulatory mechanism, which mediates tissue-specific and general resistance of rats under conditions of intermittent normobaric hypoxia. These effects did not depend on oxygenation of the inhaled gas mixture during the inter-hypoxic period.


Asunto(s)
Hipoxia Encefálica/enzimología , Mitocondrias/enzimología , Animales , Corteza Cerebral/enzimología , Transporte de Electrón/efectos de los fármacos , Cinética , Masculino , NADH Deshidrogenasa/metabolismo , Ratas , Rotenona/farmacología , Succinato Citocromo c Oxidorreductasa/metabolismo
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