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51.
The analgesic actions of some synthetically prepared peptides having the Tyr-D-Arg unit at the N terminal portion of met- and leu-enkephalin were measured by the intra-cisternal injection method in mice. Among them, Tyr-D-Arg-Gly-Phe (DR-4) induced the most potent naloxone-reversible analgesia and was also effective by s.c. injection. DR-4 showed the good affinity to mu-receptor, and the resistance to the enzymatic degradation. 相似文献
52.
Takahiro Kobayashi Ikuo Morita Sei-Itsu Murota 《Prostaglandins & other lipid mediators》1983,26(2):303-310
Effects of nitrogen dioxide (NO2) exposure on prostacyclin (PGIP2) synthesis in the rat lung and thromboxane A2 (TXA2) synthesis in the platelets were studied. Male Wistar rats were exposed to 10 ppm NO2 for 1, 3, 5, 7 and 14 days. PGI2 synthesizing activity of homogenized lung decreased. The damage of PGI2 synthesizing activity reaches its maximum at 3 days. At 14 days, PGI2 synthesizing activity returned to the normal level. The activity of PGI2 synthetase decreased significantly. The formation of lipid peroxides due to NO2 exposure may cause the depression of PGI2 synthesizing activity of lung. On the other hand, platelet TXA2 synthesizing activity increased. This increased TXA2 synthesizing activity lasted at least till 3 days. Then, it returned to the normal level. The counts of platelet were decreased significantly by 1, 3, 5 and 7 days NO2 exposure. Then the decreased counts of platelet returned to the normal level at 14 days NO2 exposure. These results indicate that the depression of PGI2 synthesizing activity lung by NO2 exposure cause an increase in TXA2 synthesizing activity of platelets. It may contribute to induce platelet aggregation and to the observed decrease in the number of platelets during NO2 exposure. 相似文献
53.
A E Mast J J Enghild H Nagase K Suzuki S V Pizzo G Salvesen 《The Journal of biological chemistry》1991,266(24):15810-15816
Serpins encompass a superfamily of proteinase inhibitors that regulate many of the serine proteinases involved in inflammation and hemostasis. In vitro, many serpins are catalytically inactivated by proteinases that they do not inhibit, leading to the concept of proteolytic down-regulation of serpin inhibitory capacity. The extent to which down-regulation of serpin activity occurs in vivo is debated, since little is known of the rates at which the process occurs. To address this debate, we have measured the rates of inactivation of three serpins, alpha 1-proteinase inhibitor (alpha 1PI), alpha 1-antichymotrypsin (alpha 1ACT), and antithrombin III (ATIII), by three human matrix metalloproteinases (MMPs-1, -2, and -3) thought to be involved in tissue destruction and repair. Our object was to establish a working kinetic model which can be used to predict whether serpin inactivation by these proteinases is likely to occur in vivo. We determined the rates of inactivation of these three serpins by each of the MMPs and compared these to rates of inhibition of the MMPs by an endogenous inhibitor, alpha 2-macroglobulin. An equation designed to predict the extent of substrate hydrolyzed by an enzyme in the presence of an enzyme inhibitor gave the following predictions of the inactivation in vivo: (i) ATIII is unlikely to be inactivated by the MMPs. (ii) MMP-2 (72-kDa gelatinase/type IV collagenase) is unlikely to inactivate any of the three serpins. (iii) MMP-1 (tissue collagenase) will inactivate alpha 1PI and alpha 1ACT only when its concentration saturates that of its controlling inhibitors. (iv) MMP-3 (stromelysin) may inactivate small amounts of alpha 1PI and more significant amounts of alpha 1ACT, even in the presence of its controlling inhibitors. Any physiologic or pathologic inactivation of these serpins by these MMPs that occurs in vivo will probably be due to MMP-3, and will likely only take place in tissues and inflammatory loci where the concentration of MMP inhibitors is depressed. 相似文献
54.
Seventy-one male and 52 female F 344 rats with leukemia used as controls in the 30-month inhalation studies were characterized by hematological and clinico-biochemical findings. Hematological findings revealed that the leukocyte count, mean corpuscular volume, and mean corpuscular hemoglobin increased in both sexes of leukemic rats showing profound anemia, while the platelet count, erythrocyte count, hematocrit, and hemoglobin concentration decreased. In these rats, the serum levels of low density lipoprotein, free cholesterol, total bilirubin, blood urea nitrogen, and triglyceride and the activities of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, creatine phosphokinase, alkaline phosphatase, and lactate dehydrogenase increased markedly and the level of high density lipoprotein, the oxygen partial pressure, and the cholinesterase activity decreased. Clinical signs such as decrease in redness of the eyes, decrease in body weight, abdominal distension, staining of the public region, and debility were seen in most leukemic animals. These clinical signs and hematological and clinico-biochemical findings may be helpful in diagnosis of leukemia in long-term experiments. 相似文献
55.
Nobutoshi Baba Hiroyuki Kawami Yukio Sato Takahiro Takayama Tetsuya Toge 《Biotherapy》1991,3(4):359-364
The enhancement of antitumor activities of the tumoricidal soluble factor (SF) from a streptococcal preparation (OK-432)-activated macrophages by the pretreatment with a protein-bound polysaccharide (PSK) was investigated in tumor-bearing mice.Two-step stimulations with OK-432 atin vivo priming andin vitro eliciting were required for the production of the tumoricidal SF by macrophages, and the tumoricidal activity of the SF apparently correlated with the uptake of OK-432 by macrophages at priming phase.Tumoricidal activity of the SF from OK-432-activated macrophages in proteose-peptone (P-P)-pretreated mice significantly decreased with the development of the tumor, whereas in PSK-pretreated mice did not. Pretreatment of tumor-bearing mice with PSK saved a decrease in the macrophages carrying Iak or asialo GM1 antigens and an increase in wheat germ agglutinin (WGA) receptors. Furthermore, the uptake of OK-432 by macrophages at priming phase was enhanced. The tumoricidal activity of the SF from OK-432-activated macrophages was augmented.Thus, PSK may restore the depressed functions of macrophages, and the combination therapy with PSK and OK-432 may be effective to enhance the production of tumoricidal SF in tumor-bearing mice. 相似文献
56.
Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin) 总被引:21,自引:0,他引:21
The mechanism of activation of tissue procollagenase by matrix metalloproteinase 3 (MMP-3)/stromelysin was investigated by kinetic and sequence analyses. MMP-3 slowly activated procollagenase by cleavage of the Gln80-Phe81 bond to generate a fully active collagenase of Mr = 41,000. The specific collagenolytic activity of this species was 27,000 units/mg (1 unit = 1 microgram of collagen digested in 1 min at 37 degrees C). Treatment of procollagenase with plasmin or plasma kallikrein gave intermediates of Mr = 46,000. These intermediates underwent rapid autolytic activation, via cleaving the Thr64-Leu65 bond, to give a collagenase species of Mr = 43,000 that exhibited only about 15% of the maximal specific activity. Similarly, (4-aminophenyl)mercuric acetate (APMA) activated procollagenase by intramolecular cleavage of the Val67-Met68 bond to generate a collagenase species of Mr = 43,000, but with only about 25% of the maximal specific activity. Subsequent incubation of the 43,000-Mr species with MMP-3 resulted in rapid, full activation and generated the 41,000-Mr collagenase by cleaving the Gln80-Phe81 bond. In the case of the proteinase-generated 43,000-Mr species, the action of MMP-3 was approximately 24,000 times faster than that on the native procollagenase. This indicates that the removal of a portion of the propeptide of procollagenase induces conformational changes around the Gln80-Phe81 bond, rendering it readily susceptible to MMP-3 activation. Prolonged treatment of procollagenase with APMA in the absence of MMP-3 also generated a 41,000-Mr collagenase, but this species had only 40% of the full activity and contained Val82 and Leu83 as NH2 termini. Thus, cleavage of the Gln80-Phe81 bond by MMP-3 is crucial for the expression of full collagenase activity. These results suggest that the activation of procollagenase by MMP-3 is regulated by two pathways: one with direct, slow activation by MMP-3 and the other with rapid activation in conjunction with tissue and/or plasma proteinases. The latter event may explain an accelerated degradation of collagens under certain physiological and pathological conditions. 相似文献
57.
Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate 总被引:17,自引:0,他引:17
The mechanisms of activation of the precursor of human matrix metalloproteinase 3 (proMMP-3/prostromelysin) by proteinases and (4-aminophenyl)mercuric acetate (APMA) were investigated by kinetic and sequence analyses. Incubation of proMMP-3 with neutrophil elastase, plasma kallikrein, plasmin, or chymotrypsin at 37 degrees C resulted in the formation of MMP-3 of Mr = 45,000 by cleaving of the His82-Phe83 bond. Since this bond is unlikely to be cleaved by these proteinases it was postulated that an initial attack of an activator proteinase on proMMP-3 creates an intermediate form, which is then processed to a more stable form of Mr = 45,000. To test this hypothesis proMMP-3 was incubated with these serine proteinases under conditions that minimize the action of MMP-3. This led to the accumulation of major intermediates of Mr = 53,000 and two minor forms of Mr = 49,000 and 47,000. The 53,000 Mr intermediate generated by human neutrophil elastase resulted from cleavage of the Val35-Arg36 whereas plasma kallikrein cleaved the Arg36-Arg37 and Lys38-Asp39 bonds and chymotrypsin the Phe34-Val35 bond, all of which are located near the middle of the propeptide. Conversion of these intermediates to the fully active 45,000 Mr form of MMP-3 resulted from a bimolecular reaction of the intermediates. A similar short-lived intermediate of Mr = 46,000 generated by APMA was a result of the intramolecular cleavage of the Glu68-Val69 bond, and it was then converted to a stable MMP-3 of Mr = 45,000 by a intermolecular reaction of MMP-3. However, MMP-3 failed to activate proMMP-3.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
58.
A new rapid and simple method has been developed for the separation of disaccharides obtained by chondroitinase digestion of chondroitin sulfates and dermatan sulfate using electrophoresis on cellulose acetate plates (Titan III cellulose acetate plates). Three disaccharides are completely separated by electrophoresis in barium acetate or calcium acetate in a short time, and less than 50 μg of glycosaminoglycan samples can be analyzed within 2 h. 相似文献
59.
Small circular DNA complexes in eucaryotic cells 总被引:7,自引:0,他引:7
A small number of eucaryotic cells (100 to 1000 cells) were pressed by mica sheet; then the extruded contents were adsorbed on mica and processed for electron microscopy. In the absence of divalent cation, small polydisperse circular DNA molecules bound to proteins or membrane material were preferentially adsorbed. The small circular DNA complexes have been found in every eucaryotic cell, primary lymphoid tissue cells of bursa and thymus, primary cell lines of retina and liver, and established cultured cell lines of embryonal teratocarcinoma, F9 and PCC3, HeLa and 3T6. Size distribution of these DNA complexes varies, depending on the cell source. The circles less than 1 μm in contour length predominate in cultured cell lines and the larger ones in primary cell lines and cells in situ. Polydisperse covalently closed circular DNAs were recovered from thymus lymphocytes by the conventional dye-CsCl buoyant density method. Their size distribution was similar to that of the small circular DNA complexes detected by the mica-press-adsorption method. They are present in several tens to hundreds of copies per cell representing, at a maximum, 0.02% of the total cellular DNA. The possibility that small circular DNA complexes may result from gene rearrangement as well as from replicon “misfiring” (A. Varshavsky, 1981, Proc. Nat. Acad. Sci. USA 78, 3673–3677) are discussed. 相似文献
60.