Voprosy biokhimii mozga最新文献

Pregnant mice at the 15th day of gestation were injected with a single intravenous dose of ENU/80 mg/kg of body weight). The protein composition of the myelin fraction isolated by means of differential centrifugation from brains of the offsprings was studied. The results obtained lead to the following conclusions: 1. The myelin protein spectrum of transplacentally intoxicated animals aged 40 days postnatal, shows decreased percentages of the Wolfgram protein and of the low molecular weight basic protein, whereas the proportions of the high molecular weight component of the myelin basic protein as well that of the Agrawal's protein are elevated. 2. The alterations in the profile of myelin proteins obtained from experimental mice aged 70 days postnatal are less severe and consist in a decline of the percentage of Wolfgrams protein and elevation of the Agrawal's protein content. 3. The intraplacental intoxication of mouse fetuses leads to development of animals defective with respect to the protein composition of the central myelin.

The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone "C" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.

Amidation of two protein fractions of brain, heart and liver of senite rats was found to decrease by 15--21% as compared with that of young animals. This decrease was shown to be due to unstable amide groups. Strong evidence is presented favouring the preposition that in proteins the unstable amide groups are those of asparagine and the stable ones those of glutamine. The possibility of the nonenzymatic deamidation of proteins was investigated. Deaminated proteins were found to be more easily attacked by proteinases which could be one of the possible ways of breakdown of aging proteins.

The present report concerns the study of the catalytic properties and the coenzyme affinity of glutamate dehydrogenase (GDH) and its isoenzymes in various preparations of the brain and liver as well as the different regulatory mechanisms controlling the ratio of the rates of biogenesis and breakdown of glutamate (Glu). The investigations carried out showed that GDH activity of various preparations of brain and liver (crystalline enzymes, cellular extracts and mitochondria) are markedly different from each other by their catalytic and regulatory properties as well as by their coenzyme activity. The data obtained make us conclude that nicotinamide-hypoxanthine-nucleotide (deaminoNAD) is a more effective coenzyme in the oxidative deamination of Glu, than other piridine nucleotides (NAD, NADP, deamino-NADP). It is supposed that in the formation of ammonia and amino acids in brain and especially liver, together with other known mechanisms an important role may be ascribed to the process of transdeamination. In this aspect, as a co-factor of oxidative deamination of Glu deamino-NAD (D-NAD) is thought to be of significant importance.

The nuclear pore complexes of cells of the superficial layers of the cerebral cortex of mice were studied by freezeetch technique from the 18--20th embryonic to 180th postnatal day. The nuclear membrane was found to be randomly penetrated by pore complexes in all age groups studied. The pores have a typical octagonal shape. The density of pores (per/um2) amounted to 7.8, 14.0, 17.0, 18.1 and 14.1 on 18--20th embryonic and 8th, 15th, 50th and 180th postnatal day respectively. The total number of pores per nucleus amounted to 1257, 6582, 5405 and 3384 on the 18--20th embryonic and the 15th, 50th and 180th postnatal day respectively. Thus the total number of pores per nucleus increases 5.2 times from the 18th--20th prenatal to the 15th postnatal day and than slightly decreases toward the 180th postnatal day. The density of pore complexes in adult brain cell nuclei is therefore very high in comparison with other normal somatic and cancer cells.

The distribution of proteolipids (PL) was studied in various parts of the nervous system of certain mammals and subcellular structures of rat brain. Soluble PL of various degrees of purification from lipids have been obtained from gray and white matter of cerebral hemispheres of cattle as well as from mitochondrial, synaptosomal and two myelin fractions of rat brain. Certain properties, protein and lipid composition and molecular weight of the PL isolated have been studied. Together with some general properties certain differences have been observed in the protein and especially in the phospholipid composition of PL isolated from the grey and white matters and subcellular particles. The PL of white matter and myelin are similar to each other in their protein and phospholipid composition but are different from those of grey matter and mitochondria, the latter in turn being also similar in their protein and phospholipid composition. The data obtained make the existence of at least two types of PL probable: one in myelin and another in mitochondria. The first is characterised by the presence of a protein corresponding to DM-20 of molecular weight of 29000, besides the main PL protein of 35-36000 molecular weight, as well as by the predominance of phosphatidylserine which forms 61% of phospholipids bound to PL. The second is characterized by the existence of one main protein corresponding to PL but of a somewhat higher molecular weight (39--40000). The phospholipid composition of the PL is rich in cardiolipin which form 38--46% of bound phospholipids.

The chronic administration of large doses of oestrogens to rats results in an increase in the weight of the adenohypophysis, in the thyroxine-binding capacity of the adenohypophyseal proteins and in the serum ceruloplasmin level. Testosterone, ant-oestrogens and an excess dose of the thyroid hormones cause parallel inhibition of all three reactions. The dopaminergic neuron blocker Pimozide potentiates all three reactions, while perphenazine, in the tested doses potentiated only the adenohypophyseal reactions. In the tested doses, dopaminergic neuron stimulators (ergocornine and analogous substances) inhibited only the adenohypophyseal reactions. The nature of the relationships between the three reactions in question is considered.

Specific proteins and phosphopeptides of nervous tissue soluble in acidified organic solvents have been shown to have an active participation in the metabolism of ammonia. Nitrogen phosphopeptides (amides) bound to phosphate residues which are non stable in acids. It was shown that acid-labil nitrogen (amide group) of phosphopeptides, bound to phosphate risidue, participates in the metabolism of ammonia formed during the oxidative deamination of amino acids. The data obtained indicate that 3'--5'-AMP dependent proteinkinase participates in the phosphorilation of phosphopeptides.