RESUMEN
Methods of infrared (IR) spectroscopy and circular dichroism (CD) are suitable techniques for detection of proteins structural changes. These methods were used for determinating peculiarities of the secondary structure of serum albumins in some representatives of two classes of reptiles: Horsfield's tortoise (Testudo horsfieldi), water snake (Natrix tessellata) and grass snake (Natrix natrix) and birds: domestic goose (Anser anser), domestic chicken (Gallus domesticus), domestic duck (Anas platyrhyncha) and dove colored (Columba livia). An analysis of IR spectra and spectra obtained by the method of CD of serum albumins of both classes representatives revealed that beta-folding structure and alpha-helical sections that form the alpha-conformation play an important role in conformational structure formation of polypeptide chain and also disordered sites of molecules of these proteins. It was observed that certain redistribution depending on animals species exists, in the formation of secondary structure of serum albumins of the investigated representatives of reptiles and birds classes between the content of beta-folding structure, alpha-helical sections and disordered sites in molecules of these proteins.
Asunto(s)
Aves/sangre , Reptiles/sangre , Albúmina Sérica , Animales , Dicroismo Circular , Estructura Secundaria de Proteína , Albúmina Sérica/análisis , Albúmina Sérica/química , Especificidad de la Especie , Espectrofotometría InfrarrojaRESUMEN
Type 1 diabetes (TID) results from the destruction of pancreatic beta-cells. In spite of genetic pre-disposition, being the major component for the development of this type of diabetes, nongenetic factors also play an important role in the disease development. Among these factors viruses are implicated in the pathogenesis of TID. Basing on the literature data we have attempted to elucidate possible role of viruses in TID pathogenesis. Viruses may be involved in the TID pathogenesis in at least two distinct mechanisms. Firstly, viruses may trigger beta-cell-specific autoimmunity with or without direct infection of beta-cells. Secondly, viruses may directly infect and destroy beta-cells resulting in TID. Moreover viruses not only cause diabetes, but also may prevent from the disease in animals susceptible to diabetes. Further studies are necessary to understand the mechanisms of the pathogenesis of human virus-induced TID.
Asunto(s)
Diabetes Mellitus Experimental/virología , Diabetes Mellitus Tipo 1/virología , Virosis/complicaciones , Animales , Autoinmunidad/inmunología , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/inmunología , Modelos Animales de Enfermedad , Humanos , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/virología , Virosis/inmunología , Virosis/virologíaRESUMEN
The effect of administration of 3-acetylpyridine (antivitamin B3), on rat brain serotoninergic and NAD receptor systems was investigated. The injection of 3-acetylpyridine to rats caused a decrease of NAD and serotonin content in the brain and changes in [U-14C]NAD binding to synaptic membranes, serotonin uptake by nerve endings, as well as sensitivity of this process to NAD (10-5 M). Pretreatment of animals with nicotinamide restored modulating effect of NAD.
Asunto(s)
Encéfalo/efectos de los fármacos , NAD/metabolismo , Piridinas/farmacología , Serotonina/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Masculino , Niacinamida/antagonistas & inhibidores , Niacinamida/deficiencia , Niacinamida/farmacología , Unión Proteica , Ratas , Ratas Wistar , Membranas Sinápticas/metabolismo , Sinaptosomas/metabolismoRESUMEN
Streptosotocin-induced diabetes in rats is accompanied by the development of diabetic complications such as neuropathies. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation. Aldose reductase inhibitors (AL-1576, sorbinil) administration leads to partial restoration of serotonin and GABA release, while picamilon restored only GABA release. It was shown that Na+,K(+)-ATPase activities decreased in synaptosomes, synaptic membranes and sciatic nerve of diabetic rats compared to control. Administration of AL-1576 normalized Na+, K(+)-ATPase activity, while sorbinil and picamilon less effectively. Sorbitol level are increased in streptozotocin-diabetic rats as compared to control. The picamilon and aldose reductase inhibitors administration to diabetic rats is accompanied by the partial reduction of brain sorbitol level. The findings confirm the important role of picamilon and aldose reductase inhibitors in the prevention and treatment of diabetic neuropathy.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Neuropatías Diabéticas/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Fluorenos/uso terapéutico , Hidantoínas/uso terapéutico , Nootrópicos/uso terapéutico , Ácido gamma-Aminobutírico/análogos & derivados , Animales , Encéfalo/metabolismo , Neuropatías Diabéticas/metabolismo , Masculino , Ratas , Ratas Wistar , Serotonina/metabolismo , Sorbitol/metabolismo , Sinaptosomas/metabolismo , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Streptozotocin-induced diabetes in rats is accompanied by development of diabetic complications such as neuropathies. It was shown that aldose reductase inhibitors (A1-1576, sorbinil and unithiol) administration partially normalized not only polyol pathway. Aldose reductase inhibitors partially restored Na+, K(+)-ATP-ase activity in sciatic nerve of diabetic rats and redox state of nicotinamide adenine dinucleotides. The sorbitol level increases in streptozotocin-diabetic rats as compared to control. Administration of aldose reductase inhibitors to diabetic rats is accompanied by partial reduction of sorbitol level in sciatic nerve. The results obtained confirm the important role of a dose reductase inhibitors, as antidiabetic drugs, in the improvement of diabetic neuropathy.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Imidazolidinas , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Neuropatías Diabéticas/metabolismo , Evaluación Preclínica de Medicamentos , Fluorenos/uso terapéutico , Glucosa/metabolismo , Hidantoínas/uso terapéutico , Imidazoles/uso terapéutico , Masculino , NADP/metabolismo , Oxidación-Reducción , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Unitiol/uso terapéuticoRESUMEN
Participation of nicotinic acid and its derivates in the functioning of nervous system is considered basing on the data from literature. It is supposed that the favourable therapeutic effects of nicotinamide, nicotinic acid and their active biological form--NAD are realized due to the mechanisms of their functioning in the nervous system, for treating schizophrenia, epilepsy and other diseases of the nervous system.
Asunto(s)
NAD/fisiología , Enfermedades del Sistema Nervioso/fisiopatología , Niacina/fisiología , Niacinamida/fisiología , Humanos , NAD/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Niacina/uso terapéutico , Niacinamida/uso terapéutico , Tranquilizantes/uso terapéuticoRESUMEN
Studies of neurotransmitter uptake and release by isolated rats brain cortex synaptosomes demonstrated that [2-14C]serotonin uptake was by 41% lower in streptozotocin-diabetic rats as compared to control. The [U-14C]GABA uptake was considerably elevated. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation, especially during the first 3 minutes. Nicotinamide (NAm) administration (200 mg/kg body weight daily, 14 days) to diabetic rats restored synaptosomal serotonin uptake up to control levels, while the GABA uptake tended to decrease in diabetic rats. With this dose of NAm the partial restoration of serotonin and GABA release was achieved. The modulating effect of in vivo administered NAm acts via NAD which binds specifically with synaptic membranes. It has been shown that brain NAD(P)/NAD(P)H decreased while sorbitol level increased in streptozotocin-diabetic rats as compared to control. The NAm administration to diabetic rats is accompanied by the increase of NAD(P)/NAD(P)H and the reduction of brain sorbitol level. Data obtained confirm the important role of NAm in the pathogenesis of diabetic encephalopathies.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Niacinamida/farmacología , Serotonina/metabolismo , Sinaptosomas/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo , Animales , Corteza Cerebral/metabolismo , Corteza Cerebral/ultraestructura , Diabetes Mellitus Experimental/patología , Masculino , NAD/fisiología , NADP/fisiología , Oxidación-Reducción , Ratas , Ratas Wistar , Sinaptosomas/metabolismoRESUMEN
NAD has been studied for its effect on the uptake of serotonin, norepinephrine, dopamine and GABA by synaptic vesicles. It has been shown that norepinephrine and dopamine uptake is not altered by addition of 10(-3) M, 10(-6) M, 10(-8) M, 10(-9) M and 10(-12) M NAD concentrations to incubation medium while the serotonin uptake is increased by 29, 47, 23, 24 and 18%, respectively. 10(-3) M and 10(-6) M NAD concentrations decrease GABA uptake by 30% and 24%. The study of 10(-6) M NAD effect on serotonin release from serotonin pre-loaded vesicles demonstrated the marked elevation of the neurotransmitter release, especially during the first 4 minutes of incubation (by 40%). The similar effect on serotonin release, is observed after addition of KCl, standard depolarizing agent, to the incubation medium. In contrast to synaptic membranes, the red blood cell membranes did not activate the neurotransmitter release after addition of serotonin pre-loaded vesicles to incubation medium, which proves the specificity of synaptic vesicles--synaptic membranes interaction. The modulating NAD action at the presynaptic membrane level can also be assumed.
Asunto(s)
Encéfalo/efectos de los fármacos , NAD/farmacología , Neurotransmisores/metabolismo , Vesículas Sinápticas/efectos de los fármacos , Animales , Encéfalo/metabolismo , Masculino , Ratas , Ratas Wistar , Vesículas Sinápticas/metabolismoRESUMEN
Content of nicotinamide nucleotides, reception of NAD by synaptic membranes and the system of 14C-serotonin uptake and liberation in rat brain nerve endings were studied under various conditions of vitamin PP consumption. In PP hypovitaminosis binding of 14C-NAD was decreased in synaptic membranes as a result of alterations in capacity of receptor sites, which occurred simultaneously with low level of nicotinamide coenzymes in rat brain. These alterations led to deterioration of NAD modulating function in liberation of 14C-serotonin from synaptosomes. The data obtained suggest that functional activity of NAD-receptor system in synaptic membranes of rat brain depends on the rate of vitamin PP consumption. These results might be considered in clinical research when vitamin PP is used for treatment of various diseases.
Asunto(s)
Encéfalo/metabolismo , Niacinamida/metabolismo , Animales , NAD/metabolismo , Niacinamida/administración & dosificación , Ratas , Serotonina/metabolismo , Sinapsis/metabolismo , Sinaptosomas/metabolismoRESUMEN
The binding of [14C]NAD to rat brain synaptic membranes is reversible and depends on incubation time, temperature and protein concentration in the reaction mixture. The value of the rate constant for [14C]NAD binding to the synaptic membranes at 24 degrees C (kl) is 1.1 X 10(-6) M-1 S-1, the rate constant for dissociation of the [14C]NAD-receptor complex (k-1) is 3.3 X 10(-3) S-1. The value of the constant for the ligand dissociation from this complex (Kd) is 3.0 nmole. Treatment of the experimental results in the Scatchard plots for the equilibrium binding of [14C]NAD to the synaptic membranes demonstrated that the receptor sites with high and low affinities for the ligand (Kd1 = 3.3 nmol, Kd2 = 14.4 nmole) and with binding capacities of 44 and 77 pmole of [14C]NAD, respectively. It was found that the synaptosomal membrane components which bind the labelled NAD have a protein nature. Data from [14C]NAD and [nicotinamide-3H]NAD binding suggest that brain synaptic membranes bind NAD at the nicotinamide and adenylic moieties.
Asunto(s)
Encéfalo/metabolismo , NAD/metabolismo , Membranas Sinápticas/metabolismo , Animales , Radioisótopos de Carbono , Cinética , Masculino , RatasRESUMEN
The paper deals with the redox state of free nicotinamide adenine dinucleotides (the NAD+/NADH ratio) in main compartments of the rat and guinea pig liver cells. NAD-pairs of cytoplasm and mitochondria in guinea pigs liver are shown to be more reduced than those in rats' liver. Stimulation of glucogenesis decreases the NAD+/NADH ratio in both compartments of rat liver and increases it in the guinea pigs' liver mitochondria. The guinea pigs' liver mitochondria synthesize actively phosphoenol pyruvate from oxaloacetate, malate and alpha-ketoglutarate. A decrease in the NAD+/NADH ratio value with introduction of beta-oxybutyrate into the incubation medium inhibits the phosphenolpyruvate synthesis from malate by 73%.
Asunto(s)
Gluconeogénesis , Hígado/metabolismo , NAD/metabolismo , Fosfoenolpiruvato/biosíntesis , Animales , Citoplasma/metabolismo , Cobayas , Hidroxibutiratos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Malatos/metabolismo , Masculino , Mitocondrias Hepáticas/metabolismo , Oxaloacetatos/metabolismo , Oxidación-Reducción , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , RatasRESUMEN
Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Hipoglucemia/inducido químicamente , Hígado/metabolismo , Niacinamida/farmacología , Animales , Depresión Química , Gluconeogénesis/efectos de los fármacos , Glucólisis/efectos de los fármacos , NAD/metabolismo , NADP/metabolismo , Ratas , Estimulación QuímicaRESUMEN
Inclusion of 1,3-butandiol as a synthetic source of nutritional energy into the composition of a low-carbohydrate diet produced a fall in the ration of free [NAD+]:[NADN] and [NADP]:[NADPN] calculated for the cytoplasm and mitochondria of the liver cell in rats according to the concentration of oxidated and reduced metabolites and the equilibrium constant of the lactate-dehydrogenase, glutamate-dehydrogenase and malic-fermentative systems. In these conditions the concentration of metabolites, at whose level the conjugation of the carbohydrates decomposition during glycolysis and their synthesis at the time of gluconeogenesis (phosphoenol-pyruvate, malate, oxaloacetate) is realized, as well as the activity of key gluconeogenesis enzymes (phosphoenol-pyruvate carboxykinase, fructose-1,6-diphosphatase) increase. The NADN generation in the course of oxidative metabolism of 1,3-butandiol gives rise to reducing properties of the free NAD-par cytoplasm and mitochondria pool, which leads to the intensification of gluconeogenesis in the liver, attended by a drop of the phosphate potential level.