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31.
32.
Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation 总被引:9,自引:0,他引:9
S Chandrasekhar A K Harvey 《Biochemical and biophysical research communications》1988,157(3):1352-1359
Treatment of chondrocytes in culture with interleukin-1 results in the production of neutral proteases that cause the degradation of the large aggregating proteoglycan. TGF-beta is a pleiotropic growth factor that has been shown to induce differentiation of cartilage and, in some cases, was able to inhibit the IL-1-dependent processes. In this report, we examined whether TGF-beta could block the IL-1 induced catabolic effects on chondrocytes. After treatment with IL-1 beta (30 ng/ml), rabbit articular chondrocytes produced approximately 2 units of neutral protease activity. Under identical conditions, TGF-beta 1 alone did not induce any protease activity. However, a combination of IL-1 and TGF-beta resulted in a dramatic reduction in the level of protease activity. The inhibitory effect of TGF-beta was also observed at the level of proteoglycan incorporation into the extracellular matrix. The IL-1 treated chondrocytes failed to incorporate proteoglycans into their extracellular matrix. However, addition of TGF-beta in the presence of IL-1 resulted in partial reversal towards a normal extracellular matrix. These studies indicate that TGF-beta can block and at least partially inhibit the catabolic effects of IL-1 on chondrocytes. 相似文献
33.
Base-sequence dependence of noncovalent complex formation and reactivity of benzo[a]pyrene diol epoxide with polynucleotides 总被引:1,自引:0,他引:1
The base-sequence selectivity of the noncovalent binding of (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyr ene (BPDE) to a series of synthetic polynucleotides in aqueous solutions (5 mM sodium cacodylate buffer, 20 mM NaCl, pH 7.0, 22 degrees C) was investigated. The magnitude of a red-shifted absorbance at 353 nm, attributed to intercalative complex formation, was utilized to determine values of the association constant Kic. Intercalation in the alternating pyridine-purine polymers poly(dA-dT).(dA-dT) (Kic = 20,000 M-1), poly(dG-dC).(dG-dC) (4200 M-1), and poly(dA-dC).(dG-dT) (9600 M-1) is distinctly favored over intercalation in their nonalternating counterparts poly(dA).(dT) (780 M-1), poly(dG).(dC) (1800 M-1), and poly(dA-dG).(dT-dC) (5400 M-1). Methylation at the 5-position of cytosine gives rise to a significant enhancement of intercalative binding, and Kic is 22,000 M-1 in poly(dG-m5dG).(dG-m5dC). In a number of these polynucleotides, values of Kic for pyrene qualitatively follow those exhibited by BPDE, suggesting that the pyrenyl residue in BPDE is a primary factor in determining the extent of intercalation. Both BPDE and pyrene exhibit a distinct preference for intercalating within dA-dT and dG-m5dC sequences. The catalysis of the chemical reactions of BPDE (hydrolysis to tetrols and covalent adduct formation) is enhanced significantly in the presence of each of the polynucleotides studied, particularly in the dG-containing polymers. A model in which catalysis is mediated by physical complex formation accounts well for the experimentally observed enhancement in reaction rates of BPDE in the alternating polynucleotides; however, in the nonalternating polymers a different or more complex catalysis mechanism may be operative.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
34.
Concentrations of manganese were determined in the liver, kidney, muscle and bone of white suckers (Catostomus commersoni) from five acid (pH < 5.8), and two circumneutral lakes in south-central Ontario. Manganese tissue concentrations were greater in fish captured from the most acidified lakes with the greatest concentrations of dissolved manganese. These fish had increased concentrations of manganese in the liver, as indicated by a comparison of liver:kidney manganese concentration ratios among the seven fish populations. Tissue concentrations of manganese from all populations either were negatively correlated (P < 0.05) or remained constant with fish size indicating homeostatic regulation of this metal. Manganese concentrations of the benthic fauna were positively correlated to sediment concentrations (R=0.30). Lake sediment manganese concentrations were significantly correlated to maximum lake depth (R=0.80, P < 0.03), with the concentrations in the top 0–1 cm dependent on the redox conditions in the seven lakes. Based on the seven lakes studied, manganese concentrations in the benthic-feeding white sucker correlated better with dissolved manganese, than with either the concentrations in food or surficial sediments. 相似文献
35.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4
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Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
36.
Uncoupling the red cell sodium pump by proteolysis 总被引:1,自引:0,他引:1
In situ proteolysis of Na,K-ATPase was studied using inside-out red cell membrane vesicles. Proteolysis of the enzyme in its "E1" conformation with either trypsin or chymotrypsin inactivated cation translocation more than ATP hydrolysis. This was evident both in the absence of intravesicular alkali cations when Na-ATPase was compared to ATP-dependent 22Na+ influx, and in the presence of K+ when Na+/K+ exchange was compared to (Na+ + K+)-activated ATPase. This differential loss in pump versus hydrolysis was observed also when the activities of only intact, non-leaky vesicles were compared and therefore reflects intramolecular uncoupling rather than nonspecific leakage. Although oligomycin and thimerosal, like trypsin and chymotrypsin, inhibit the enzyme's conformational step(s), neither effect uncoupling. It is concluded that specific cleavage(s) of Na,K-ATPase, at least as it exists in situ, alters the reaction sequence with respect to the normal ordered mechanism. Accordingly, cytoplasmic Na+ and extracellular K+ bind to the enzyme, stimulate phosphorylation (ATP + E1----E1P + ADP) and dephosphorylation (E2P----E2 + Pi), respectively, but each is then released to the same side from which it had bound; presumably release occurs prior to the conformational transitions of E1P to E2P and E2 to E1. This conclusion is supported by experiments showing that, ar micromolar ATP concentration, the hydrolytic activity (Na-ATPase) of the trypsinized but not the unmodified enzyme is stimulated by K+, consistent with earlier experiments (Hegyvary, C., and Post, R. L. (1971) J. Biol. Chem. 246, 5234-5240) showing that the K X E2 to K X E1 transition is slower than the E2 to E1 transition. 相似文献
37.
D J Harvey J F Godber M P Timmerman L M Castell C C Ashley 《Biochemical and biophysical research communications》1985,128(3):1180-1189
The fluorescent Ca2+ indicator, quin 2, has been used in isolated striated muscle fibres. There is a distinct quin 2 fluorescence peak at lambda 500 nm upon excitation at lambda 339 nm after axial injection of the potassium salt of quin 2, pH 7.1. Single voltage-clamp or current clamp electrical stimulation resulted in a distinct transient change in the fluorescence at lambda 500 nm which was not observed at lambda 400 nm, the peak of the fibre autofluorescence. Ca2+ buffering is marked at high quin 2 concentrations (greater than or equal to 400 microM) producing a slow decay of force and fluorescence. At lower concentrations (8-30 microM) of quin, the decay of force is within the range observed in non-injected control fibres. A Kd of 457 nM at 5 mM free Mg2+ suggests an upper resting free Ca2+ concentration of 310 nM at 12 degrees C. 相似文献
38.
T R Hall R W Lea S Harvey D M Vowles 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1985,82(2):423-426
Monoamine oxidase (MAO) activity was measured fluorometrically in liver, kidney, intestine and brain of adult male and female ring doves. Liver MAO was inhibited in a concentration-related fashion by clorgyline and harmaline (MAO type A inhibitors) where a plateau in the inhibition curve occurred with about 15% activity remaining, and also by the type B inhibitor deprenyl, which produced a plateau when about 85% activity remained. Kidney, intestine and brain MAO were inhibited in a biphasic manner by harmaline. Results with inhibitors suggest that 85% of liver MAO, 86% of kidney MAO, 88% of intestine and 75% of brain MAO is type A. Using 10(-6) M harmaline to differentiate between MAO-A and MAO-B type activities, the apparent maximal velocities (Vmax) and Michaelis constants (Km) were determined in different tissues. Most activity occurred in the intestine, with proportionally lesser amounts of kidney, liver and brain. The majority of MAO present was in the A form. Except for kidney, Km of MAO-B was higher than that of MAO-A. Both MAO-A and -B activities were higher in the intestines of male birds, although sex differences in content and type of MAO activity were not observed in other tissues of the ring dove. 相似文献
39.
Toxins C13S1C3 and C13S2C3 from green mamba venom (Dendroaspis angusticeps) acted like dendrotoxin to increase acetylcholine release in response to nerve stimulation in the chick biventer cervicis preparation. Proteins B and E from black mamba venom (Dendroaspis polylepis) had no prejunctional facilitatory activity. All four proteins are trypsin inhibitor homologues. Binding of a prejunctional facilitatory toxin (Polylepis toxin I) to motor nerves was rapid and did not require the presence of Ca2+ or nerve stimulation. Binding was not prevented by protease inhibitors that lacked facilitatory actions. Prejunctional facilitatory toxins also augmented transmitter release in the chick oesophagus and the mouse vas deferens preparations. The effects were rapid in onset and could wane spontaneously. 125I-labelled dendrotoxin bound specifically to rat brain synaptosomes with a KD of about 3 nM. Binding was prevented by native dendrotoxin but not by beta-bungarotoxin or atropine. It is concluded that prejunctional facilitatory toxins affect transmitter release at many types of nerve endings in addition to motor nerve terminals. From consideration of the structures of active and inactive molecules, it is thought that binding of the active toxins may involve several exposed lysine residues. 相似文献
40.
Sexual behavior of male offspring from female mice chronically crowded during Days 12-17 of pregnancy was investigated. In an 80-min test pairing with a sexually experienced female primed with estradiol and progesterone injections, males from crowded mothers displayed poorer copulation than controls: mount and intromission latencies were longer, number of mounts and intromissions lower, and ejaculations within the test period were abolished. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor in offspring from crowded mothers. A second series of experiments investigated the effects of ACTH treatment of females during the same period of pregnancy. A low dose rate (1 IU injected daily) had little effect but male offspring from females injected daily with 8 IU displayed longer intromission latency and fewer mounts and intromissions than controls. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor, although mount frequency remained depressed. The similarity of the effects on male offspring copulation of crowding their mothers during pregnancy or ACTH treatment during pregnancy suggest mediation by similar mechanisms, implicating involvement of maternal pituitary-adrenocortical secretions during pregnancy in the production of these behavioral deficits. Postnatal influences were minimized by fostering all litters at birth to untreated dams. 相似文献