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11.
Lipid soluble psychotropics inhibit brain PKC-catalyzed phosphorylation of exogenous and endogenous proteins to varying degrees. These drugs were better inhibitors of Ca2+/PL-dependent phosphorylation of histones (H) than that of Ca2+/PL-independent protamine sulfate (PrSO4): antidepressants/antipsychotics displayed IC50 of 0.1 to 0.16 mM towards H and 0.3 to 4.0 mM towards PrSO4 phosphorylation. Sedatives/anesthetics were less efficient inhibitors with much higher IC50 of 1.3 to 40 mM. Phosphorylation of a Ca2+-dependent but PL-independent p80 protein and of a cluster of Ca2+/PL-dependent proteins, p16-20, in brain was also inhibited by the antidepressants/antipsychotics but not by the sedatives/anesthetics. Phorbol ester binding studies revealed that these inhibitors do not compete for DAG binding site(s) on PKC. However, both drug-PL and drug-PKC interactions seem to be relevant in their mechanism of action. Furthermore, our data suggest that the hydrophobic nature of the propanamine side chain or its N-methylated version as well as the tricyclic nucleus influence drug-PKC interaction. Although many of these drugs have other accepted modes of action, modulation of PKC activity in brain, may be yet another aspect to be considered in their mechanism of action. 相似文献
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Chromosomal protein HMG-14 is overexpressed in Down syndrome. 总被引:2,自引:0,他引:2
The physical phenotype of Down syndrome, one of the most prevalent genetic disorders, results from an extra copy of regions q22.1 to q22.3 of chromosome 21 in cells of affected individuals. The gene coding for chromosomal protein HMG-14 is among the limited number of genes, coding for known functions, which has been mapped to this region of chromosome 21. Here we report a gene dosage effect on the expression of HMG-14 in both cultured cells and brain tissue samples obtained from Down syndrome patients. The putative role of HMG-14 in the structure of active chromatin raises the possibility that elevated levels of this protein may be a contributing factor in the etiology of Down syndrome. 相似文献
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M Bustin P S Becerra M P Crippa D A Lehn J M Pash J Shiloach 《Nucleic acids research》1991,19(11):3115-3121
Vectors for expressing human chromosomal proteins HMG-14 and HMG-17 in bacterial cultures under the control of the temperature-inducible lambda PL promoter have been constructed. The open reading frames of the cDNAs have been amplified by the polymerase chain reaction (PCR), utilizing amplimers containing desired restriction sites, thereby facilitating precise location of the initiation codon downstream from a ribosomal binding site. Expression of the recombinant proteins does not significantly affect bacterial growth. The rate of synthesis of the recombinant proteins is maximal during the initial stages of induction and slows down appreciably with time. After an initial burst of protein synthesis, the level of the recombinant protein in the bacterial extracts remains constant at different times following induction. Methods for rapid extraction and purification of the recombinant proteins are described. The recombinant proteins are compared to the proteins isolated from eucaryotic cells by electrophoretic mobility, Western analysis and nucleosome core mobility-shift assays. The ability of the proteins to shift the mobility of the nucleosome cores, but not that of DNA, can be used as a functional assay for these HMG proteins. A source for large quantities of human chromosomal proteins HMG-14 and HMG-17 will facilitate studies on their structure, cellular function and mechanism of interaction with nucleosomes. 相似文献