RESUMEN
We studied the influence of hypoxic-hypercapnic environment under the effect of hypothermia (artificial hibernation) on fatty acids spectrum of inner mitochondrial membrane (IMM) lipids of rat cardiomyocytes and hepatocytes. Specific for cellular organelles redistribution of IMM fatty acids was determined. It led to the reduction of total amount of saturated fatty acids (SFAs) and increase of unsaturated fatty acids (UFAs) in cardiomyocytes and to the increase of SFAs and decrease of UFAs in hepatocytes. The decrease in the content of oleic acid and increased content of arachidonic and docosahexaenoic acids in IMM were shown. This may be due to their role in the regulatory systems during hibernation, as well as following exit therefrom. It is assumed that artificial hibernation state is characterized by the stress reaction leading to optimal readjustment of fatty acids composition of membrane lipids, which supports functional activity of mitochondria in hepatocytes and cardiomyocytes.
Asunto(s)
Ácidos Grasos Insaturados/química , Ácidos Grasos/química , Hepatocitos/metabolismo , Hipercapnia/metabolismo , Hipoxia/metabolismo , Membranas Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Animales , Animales no Consanguíneos , Ácidos Grasos/clasificación , Ácidos Grasos/aislamiento & purificación , Ácidos Grasos Insaturados/clasificación , Ácidos Grasos Insaturados/aislamiento & purificación , Hibernación , Masculino , Lípidos de la Membrana/química , Lípidos de la Membrana/clasificación , Lípidos de la Membrana/aislamiento & purificación , Mitocondrias/química , Mitocondrias/metabolismo , Membranas Mitocondriales/química , Ratas , Estrés FisiológicoRESUMEN
OBJECTIVE: Study of human erythrocyte DP response under modification by activators and blockers of the functional state of Ca2+-dependent K+ channels under low rate ß-radiation. MATERIALS AND METHODS: Erythrocytes were isolated from the donor blood. The zeta potential was computed from the value of the cell electrophoretic mobility. The investigated drugs preliminary introduced in cellular suspensions, and then aliquote of 90Sr(NO3)2 solution to get the final activity concentration of 44,4kBqâ l-1. RESULTS: The radioisotope radiation of 90Sr/90Y (RR, 15 µGyâ h-1) increases an absolute value of erythrocyte membranes DP (DPab), and its action is reversible. It specifies the effect is mediated by non-ionizing part of the RR. Dibutyril-cAMP dose-independent increases DPab of erythrocyte membranes in the concentration range of 1-100 мкÐ, but RR does not amplify this effect. Anaprilin increases dose-independent DPab in concentrations 10 and 100 µÐ. The effect of maximal concentration of anaprilin (100 µÐ) decreases by RR. Clotrimazol increases DPab of erythrocyte membranes in the concentration range of 0,1-10 µÐ relatively control, while its maximal concentration - decreases, and the minimal level does not reliably influence on this index The action of Ñlotrimazol on DP in concentrations of 10-100 µÐ is abolished by RR, and is not changed in the range of 0,1-1,0 µÐ. Nitrendipine raises DPab of erythrocyte membranes in all of range of concentrations, and RR amplifies the effect of the drug. CONCLUSIONS: 1. There is a threshold of the biological action on cells for the ionizing component of radioisotope radiation determined by efficiency of operation their antioxidant system.2. At dose rates below a threshold, the action of ionizing radiation is mediated by its non-ionizing component, and is reversible, and therefore is determined only in the field of radiation.
RESUMEN
We investigated the energy activity of mitochondria from rat cardiomyocytes under the artificial carbon dioxide hypobiosis, which led to physiological changes in the organism (the decrease of body temperature, the reduction of heart rate, etc.). The respiratory and phosphorylation activities in mitochondria of cardiomyocytes is reduced when using two oxidation substrates (succinate and malate), which characterize the rate of the oxygen consumption by the mitochondria. The partial uncoupling of the oxidation and phosphorylation processes when using the malate unlike succinate was established. The activity of NADH-KoQ-oxidoreductase (complex I of the respiratory chain) is inhibited, but the activities of succinate dehydrogenase and cytochrome oxidase don't change. Probably, the priority of the succinate use under the artificial hypobiosis provides the support of the mitochondria functional activity on a sufficient energy level. It is evidenced by the ATP-synthetase activity. The modifications of the structural and functional state of the inner mitochondria membrane of the cardiomyocytes are directed to the adaptation under the artificial carbon dioxide hypobiosis.
Asunto(s)
Dióxido de Carbono/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Membranas Mitocondriales/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Oxígeno/farmacología , Animales , Animales no Consanguíneos , Temperatura Corporal/efectos de los fármacos , Fraccionamiento Celular , Transporte de Electrón/efectos de los fármacos , Transporte de Electrón/fisiología , Complejo I de Transporte de Electrón/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Hipotermia/metabolismo , Hipotermia/fisiopatología , Hipoxia/metabolismo , Hipoxia/fisiopatología , Malatos/metabolismo , Masculino , Mitocondrias Cardíacas/metabolismo , Membranas Mitocondriales/metabolismo , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Ratas , Succinato Deshidrogenasa/metabolismo , Ácido Succínico/metabolismoRESUMEN
The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.
Asunto(s)
Carcinoma Pulmonar de Lewis/metabolismo , Metabolismo Energético/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sarcoma 37/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patología , Catalasa/genética , Catalasa/metabolismo , Ácido Dicloroacético/farmacología , Metabolismo Energético/genética , Humanos , Ratones , Mitocondrias/genética , Mitocondrias/patología , Especificidad de Órganos , Estrés Oxidativo , Sarcoma 37/tratamiento farmacológico , Sarcoma 37/genética , Sarcoma 37/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
The activity of enzymes of the respiratory chain and structural-dynamic properties of the inner mitochondrial membrane (IMM) of sarcoma 37 (S37) in mice under sodium dichloroacetate (SDA) administration in a daily dose of 86 mg/kg of body weight starting from the 2nd day after tumor transplantation were investigated. The dynamic and structural state of the IMM components was determined using the fluorescent probes. With S37 growth the intensification of glycolytic metabolism occurred on the background of suppressed functional capacity of mitochondrial respiratory chain enzymes. The changes of conformational properties of protein molecules and the increase of IMM lipid phase microviscosity were shown. The administration of SDA promotes the decrease of lactate content and the increase of pyruvate dehydrogenase activity in S37. This was accompanied by further suppression of the functional activity of the respiratory chain complexes and H+-ATPase coupled with conformational modification ofprotein molecules and changes of the structural orderliness of the IMM lipid phase, possibly due to intensification of reactive oxygen species generation.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Ácido Dicloroacético/farmacología , Membranas Mitocondriales/efectos de los fármacos , Neoplasias de los Músculos/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Animales , Transporte de Electrón/efectos de los fármacos , Glucólisis/efectos de los fármacos , Cetona Oxidorreductasas/metabolismo , Ácido Láctico/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Membranas Mitocondriales/química , Membranas Mitocondriales/metabolismo , Neoplasias de los Músculos/metabolismo , Neoplasias de los Músculos/patología , Trasplante de Neoplasias , Conformación Proteica , Proteínas Serina-Treonina Quinasas/metabolismo , ATPasas de Translocación de Protón/metabolismo , Especies Reactivas de Oxígeno/agonistas , Especies Reactivas de Oxígeno/metabolismo , Sarcoma/metabolismo , Sarcoma/patología , Carga Tumoral/efectos de los fármacosRESUMEN
AIM: to study the activity of antioxidant enzymes and to evaluate an intensity of prooxidant processes in sarcoma 37 (S37) cells during tumor development and under influence of sodium dichloroacetate (SDA). METHODS: Activity of total superoxide dismutase (SOD), SOD isoforms, catalase (Cat), glutathione peroxidase (GP), and glutathione reductase (GR), as well as content of reduced glutathione (GSH) and lipid peroxidation (LP) secondary byproducts were determined in S37 homogenated tissues of untreated mice and animals treated with SDA at daily dose of 86 mg/kg. RESULTS: SDA treatment of S37-bearing mice resulted in the reduced activities of total SOD, SOD isoforms (especially Mn-SOD), Cat, GP and significantly decreased GSH content on the background of LP intensification in tumor tissue. CONCLUSION: The observed changes of oxidative homeostasis in S37-bearing animals treated with SDA could be considered as an element of antitumor action of SDA.