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61.
The molecular basis of anesthetic interaction with membrane proteins has been explored via determination of anesthetic effects on the structure and dynamics of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) β2 subunit in dodecylphosphocholine (DPC) micelles by 1H and 15N solution-state NMR. Both 1-chloro-1,2,2-trifluorocyclobutane (F3) and isoflurane, two volatile general anesthetics, induced nonuniform changes in chemical shifts among residues in TM2e. Saturation transfer difference NMR experiments further confirmed the direct anesthetic interaction with TM2e. A significant and more specific anesthetic interaction was observed on three leucine residues at the helix C-terminus. Although the TM2e helical structure remained after addition of anesthetics, plausible shortening and lengthening of helix hydrogen bonds were evidenced by periodic changes in backbone amide chemical shifts. The TM2e backbone dynamics were determined on the basis of the 15N relaxation rate constants, R1 and R2, and the 15N-[1H] NOE using the model-free approach. The global tumbling time (11.7 ns) of TM2e in micelles slightly increased (∼12.3-12.5 ns) in the presence of anesthetics. The order parameter, S2, exceeded 0.9 for all 15N-labeled residues, showing a restricted internal motion. Anesthetics appear to have minor effect on the TM2e's internal motion. This study provided the basis for subsequent more comprehensive studies of anesthetic effects on the transmembrane domain complex of neuronal nAChR. 相似文献
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A method is described for an accurate extrapolation of heart rates (HR) recorded during exercise testing to their steady-state levels attainable at every load step. The method makes it possible to study individual correlations between the HR and load power, e.g., in short-term myocardial ischemia. The load ranges over which the HR changed linearly or nonlinearly with power were found on testing 36 angina pectoris patients with transient STdepressions. The 24-hour HR minima and the threshold HR magnitudes corresponding to the aerobic thresholds of specific myocardial loci were within linear ranges, whereas the maximum attainable HR magnitudes most frequently were within nonlinear ranges. This nonlinearity is likely to be due to the onset of anaerobic processes contributing to the total energy production in the body. Hence, the point of transition to nonlinear HR changes, experimentally detectable during exercise tests with ECG monitoring, determines the anaerobic threshold. 相似文献
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5-day morning injections to pubertal male rats of polypeptide epithalamin preparation obtained from cattle epiphysis, in dose of 0.25 mg/100 g body mass induced the increase of serotonin epiphyseal concentration night peak, N-acetylserotonin and melatonin and didn't produce any essential influence on 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acid level. It has been concluded, that epiphyseal peptides and indoles interact according to ultrashort connection, epiphyseal peptides point of application is the reaction of tryptophan transformation into serotonin and its further metabolism in N-acetylserotonin and melatonin. It has been suggested that the increase of epiphyseal melatonin production is on the basis of epithalamin therapeutic action. 相似文献
67.
Medha Raina Adil Moghal Amanda Kano Mathew Jerums Paul D. Schnier Shun Luo Rohini Deshpande Pavel V. Bondarenko Henry Lin Michael Ibba 《The Journal of biological chemistry》2014,289(25):17780-17790
Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNATyr with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control. 相似文献
68.
K F Shol'ts D V Mammaev D I Bondarenko L S Lagutina 《Biokhimii?a (Moscow, Russia)》1990,55(10):1832-1840
The effect of thirteen synthetic 2-n-alkyl derivatives of malonic acid on the rate of the mitochondrial succinate oxidase reaction controlled by the dicarboxylate carrier, was studied. These compounds were shown to act as competitive inhibitors of succinate transport and could interact with the carrier according to the 1:1 stoichiometry. The affinity of the inhibitor for the carrier increased in parallel with the increase in the alkyl residue length. This dependence was impaired only in the case of pentyl-, hexyl- and heptylmalonates having close values of inhibition constants. The data obtained suggest that the polar site and two hydrophobic regions are located in the vicinity of the carrier active site. The possible organization of the carrier substrate-binding site is discussed. 相似文献
69.
A A Askalonov S M Gordienko O E Avdyunicheva A V Bondarenko S F Voronkov 《Journal of hygiene, epidemiology, microbiology, and immunology》1987,31(2):219-224
It has been demonstrated in experiments on mice (CBA X C57BL) X F1, thymectomized and irradiated by 800 R, with the haemopoietic system restored by bone marrow (B-mice) that in these animals, as compared with the controls, the changes in cellular immunity (inhibition of natural killer cells and stimulation of individual functions of the phagocytizing cells) are accompanied by considerable inhibition of osteogenesis. Compensatory regeneration of broken thigh-bone in B-mice is delayed by 5--10 days in various elements of the regenerated tissue in comparison with normal mice. Anatomical formation of the provisional callus in B-mice is not completed on day 21 and approaches a 14-day regenerate of the controls. The obtained results suggest the participation of T-system immunity in the reparatory regeneration of bone tissue. 相似文献
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