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991.
失血性休克引起大鼠肠系膜动脉平滑肌依钙K^+通道活动改变 总被引:10,自引:0,他引:10
在由股动脉放血制备的失血性休克大鼠模型急性分离的肠系膜动脉平滑肌细胞上,利用膜片箝单通道记录技术观察了血管平滑肌依钙K^ 通道(BKca)的活动,发现在对去甲肾上腺素(NE)反应性增高的休克代偿期,BKca的开放概率(P0)和单位电导都显著较正常动物的低,P0的改变主要是由通道的慢关闭时间常数(τcs)增大引起关闭时间延长所致;而处于对NE反应性降低的休克失代偿期,BKca的P0和单位电导都高于正常动物,P0的变化也主要是τcs减小所致。 相似文献
992.
肾缺血增强大鼠延髓腹外侧头端区神经元电话动和Fos蛋白表达 总被引:2,自引:0,他引:2
在67只切断两侧缓冲神经的麻醉Sprague-Dawley大鼠,应用细胞外记录的电生理方法和免疫组织化学技术,分别观察肾缺血对延髓腹外侧头端区巨细胞旁外侧核神经元自发放电活动和Fos蛋白表达的影响.所得结果如下(1)左肾动脉阻断后,28个单位的放电频率由11.40±1.08增至21.1±1.74spikes/s(P<0.001),血压和心率无明显变化(P>0.05);(2)在17个放电单位中,应用腺苷受体拮抗剂8-苯茶碱(8-phenyltheophylline,10mg/kg)可明显抑制肾缺血的兴奋效应(P<0.05);(3)肾缺血后,延髓腹外侧头端区的Fos蛋白样免疫反应神经元显著增加(P<0.01);(4)预先应用8-苯茶碱可明显减弱肾缺血所激活的Fos蛋白表达反应(P<0.05).以上结果提示肾缺血增强延髓腹外侧头端区神经元的放电活动和Fos蛋白表达,而此作用可能与肾脏缺血所产生的腺苷激活肾内感受器有关. 相似文献
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996.
Chiral trifluoromethanesulfonamide 4, diphenylphosphoramides 5 and 6, and phenylthiophosphoramide 7 were prepared from the reaction of trifluoromethanesulfonic anhydride, diphenylphosphinic chloride, and diphenylthiophosphinic chloride with (R)-(+)-1,1'-binaphthyl-2, 2'-diamine, respectively. They were used as catalytic chiral ligands in the asymmetric addition reaction of diethylzinc to aldehydes in the presence of titanium(IV) isopropoxide to give the corresponding sec-alcohols with 43-54%, 18-22%, 30-34%, and 52-64% enantiomeric excess, respectively. Copyright 2000 Wiley-Liss, Inc. 相似文献
997.
Porphyromonas gingivalis proteinases as virulence determinants in progression of periodontal diseases 总被引:7,自引:0,他引:7
Kadowaki T Nakayama K Okamoto K Abe N Baba A Shi Y Ratnayake DB Yamamoto K 《Journal of biochemistry》2000,128(2):153-159
Porphyromonas gingivalis, one of the major causative agents of periodontal diseases, produces large amounts of arginine- and lysine-specific cysteine proteinases in cell-associated and secretory forms, which are now referred to as Arg-gingipain (Rgp) and Lys-gingipain (Kgp), respectively. A number of studies have revealed that these proteinases are closely associated with the periodontopathogenesis of this bacterium: destruction of periodontal connective tissues, disruption of host defense mechanisms, and development and maintenance of inflammation in periodontal pockets. With respect to the physiology of the bacterium, Rgp and Kgp are indispensable for it to obtain nutrients from the environment, since it cannot utilize saccharides as carbon/energy sources for growth and totally depends on peptides and amino acids that are provided from environmental proteins by Rgp and Kgp. Furthermore, proteolytic activities of Rgp and Kgp contribute to processing/maturation of various cell-surface proteins of P. gingivalis, such as fimA fimbrilin (a subunit of major fimbriae), 75-kDa protein (a subunit of minor fimbriae), hemagglutinins, and the hemoglobin receptor protein, which are important for the bacterium to colonize and proliferate in the gingival crevice and to invade the periodontium. These findings strongly indicate critical roles of Rgp and Kgp in the virulence of P. gingivalis. 相似文献
998.
Liu W Ren C Shi J Feng X He Z Xu L Lan K Xie L Peng Y Fan J Kung Hf Yao KT Xu RH 《Biochemical and biophysical research communications》2000,270(1):293-297
Previously we have shown that blocking bone morphogenetic protein (BMP) receptor signaling by a dominant negative BMP receptor causes neurogenesis in Xenopus animal caps (ACs), whereas the physiological neural inducer noggin acts as a homodimer physically binding to BMP-4 and disrupting its signaling at the ligand level. The present study attempted to elucidate the relationship between the structure and function of noggin. By replacing some cysteine residues with serine residues through a site-directed mutagenesis strategy, we generated three noggin mutants, C145S, C205S, and C(218, 220, 222)S (3CS). Although mRNAs encoded by these mutants were translated as efficiently as wild-type (WT) noggin mRNA, they behaved differently when expressed in vivo. Expression of WT noggin or C205S in Xenopus ACs converted the explants (prospective ectoderm) into neural tissue, indicated by the neural-like morphology and expression of the pan neural marker NCAM in the ACs. In contrast, ACs expressing C145S or 3CS sustained an epidermal fate like the control caps. Similar results were observed in the mesoderm where C205S (but not C145S and 3CS) displayed dorsalizing activity as well as WT noggin. Altogether, our results suggest that Cys145 alone or Cys(218, 220, 222) as a whole in noggin protein is required for the biological activities of noggin, probably participating in the dimerization of noggin with BMP-4 or itself. 相似文献
999.
The allosteric activation of the T127-->L mutant of 3',5'-cyclic adenosine monophosphate (cAMP) receptor protein (CRP) by cAMP changes from an exothermic, independent two-site binding mechanism at pH 7.0 to an endothermic, interacting two-site binding mechanism at pH 5.2, similar to that observed for CRP at pH 7.0 and 5.2. Since the T127-->L mutation at the subunit interface of the CRP dimer creates a more perfect leucine-zipper motif, it is believed to increase the intersubunit association and the stability of the CRP, as is observed by the higher thermal stability of the T127L mutant relative to that of CRP in differential scanning calorimetry (DSC) measurements. The DSC scans also exhibit a single thermal denaturation transition for CRP and a S128A mutant from pH 5.2 to 7. 0, while the broader transition peak of the T127L mutant becomes resolvable into two transitions below pH < or =5.2. Circular dichroism measurements on T127L and CRP at pH 7.0 and 5.2 show changes in the tertiary structure of both proteins with the exception of the tertiary structure around the two tryptophan residues in the amino-terminal domain. Although gel electrophoresis of the proteolysis (pH 5.2) products of T127L, CRP, and their cAMP- and cGMP-ligated complexes shows the subunit band and an amino-terminal domain fragment band, the fully allosterically activated complexes of T127L and CRP show the amino-terminal domain fragment band but not the subunit band. The results are interpreted in terms of the allosteric activation of CRP by cAMP by a conformational change from an "open" to a "closed" form of CRP, which involves changes in the tertiary structure of the carboxyl-terminal domains that are partially induced by an increase in the intersubunit association in T127L. While T127L retains its intersubunit association from pH 5.2 to 7.0, changes occur in the carboxyl-terminal domain so that the endothermic, allosteric activation mechanism of CRP by cAMP is restored in T127L at pH 5.2. 相似文献
1000.
Luke C Schick C Tsu C Whisstock JC Irving JA Brömme D Juliano L Shi GP Chapman HA Silverman GA 《Biochemistry》2000,39(24):7081-7091
The human squamous cell carcinoma antigens (SCCA) 1 and 2 are members of the serpin family that are 92% identical in their amino acid sequence. Despite this similarity, they inhibit distinct classes of proteinases. SCCA1 neutralizes the papain-like cysteine proteinases, cathepsins (cat) S, L, and K; and SCCA2 inhibits the chymotrypsin-like serine proteinases, catG and human mast cell chymase. SCCA2 also can inhibit catS, as well as other papain-like cysteine proteinases, albeit at a rate 50-fold less than that of SCCA1. Analysis of the mechanism of inhibition by SCCA1 revealed that the reactive site loop (RSL) is important for cysteine proteinase inhibition. The inhibition of catS by a mutant SCCA2 containing the RSL of SCCA1 is comparable to that of wild-type SCCA1. This finding suggested that there were no motifs outside and only eight residues within the RSL that were directing catS-specific inhibition. The purpose of this study was to determine which of these residues might account for the marked difference in the ability of SCCA1 and SCCA2 to inhibit papain-like cysteine proteinases. SCCA2 molecules containing different RSL mutations showed that no single amino acid substitution could convert SCCA2 into a more potent cysteine proteinase inhibitor. Rather, different combinations of mutations led to incremental increases in catS inhibitory activity with residues in four positions (P1, P3', P4', and P11') accounting for 80% of the difference in activity between SCCA1 and SCCA2. Interestingly, the RSL cleavage site differed between wild-type SCCA2 and this mutant. Moreover, these data established the importance of a Pro residue in the P3' position for efficient inhibition of catS by both wild-type SCCA1 and mutated SCCA2. Molecular modeling studies suggested that this residue might facilitate positioning of the RSL within the active site of the cysteine proteinase. 相似文献