Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structure of tRNAVal2a from baker's yeast has been determined. The general methods of the investigation are presented. Twenty six distinguished points can be noted in the tRNAVal2a and tRNA1Val from baker's yeast. The anticodon region of tRNAVal2a is represented by the sequence NAC, where N corresponds to a uridine analogue nucleoside of unknown structure. The comparison of primary structures of tRNAVal2a, tRNAVal2a, tRNA1Val from E. coli and tRNAVal2a and tRNA1Val from baker's yeast is analysed.
Mol Biol (Mosk)
PMID:[The primary structure of tRNA Val 2a from baker's yeast]. 121 73

N-Acetylcysteine (NAC), a cysteine derivative with chemoprotective and radioprotective effects, was found to elevate bovine pulmonary artery endothelial cell (EC) glutathione after in vitro incubation. The elevation in glutathione was associated with enhanced uptake of radioactivity of cystine from the medium. Because cystine in medium was converted rapidly to cysteine and cysteinyl-NAC in the presence of NAC and given that cysteine has a higher affinity for uptake by EC than cystine, we conclude that the enhanced uptake of radioactivity was in the form of cysteine and at least part of the stimulatory effect of NAC on EC glutathione was due to a formation of cysteine by a mixed disulfide reaction of NAC with cystine similar to that previously reported for Chinese hamster ovarian cells (R. D. Issels et al. 1988. Biochem. Pharmacol. 37:881-888). However, NAC was more effective than cysteine in elevating cellular glutathione at equimolar concentrations, and at higher concentrations of NAC an elevation of EC glutathione occurred even in the absence of cystine in the medium through a currently unknown mechanism. Thus, at least two mechanisms are operative in the elevation of endothelial cellular glutathione by NAC. NAC may be a useful compound for elevating glutathione of the pulmonary vasculature for protection against oxidant stress.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Elevation of glutathione levels in bovine pulmonary artery endothelial cells by N-acetylcysteine. 152 Apr 92

The NAC (nitrogen assimilation control) protein from Klebsiella aerogenes is a LysR-like regulator for transcription of several operons involved in nitrogen metabolism, and couples the transcription of these sigma 70-dependent operons to regulation by the sigma 54-dependent NTR system. NAC activates expression of operons (e.g. histidine utilization, hut), allowing use of poor nitrogen sources, and represses expression of operons (e.g. glutamate dehydrogenase, gdh) allowing assimilation of the preferred nitrogen source, ammonium. NAC is both necessary and sufficient to activate transcription, but the expression of the nac gene is totally dependent on the central nitrogen regulatory system (NTR) and RNA polymerase carrying the sigma 54 sigma factor (RNAP sigma 54). Nitrogen starvation signals the NTR system to transcribe nac, and NAC activates the transcription of hut, put (proline utilization), and urease. NAC does not affect the transcription of RNAP sigma 54-dependent operons like ginA or nifLA, which respond directly to the NTR system, but activates transcription of RNAP sigma 70-dependent operons. Thus NAC acts as a bridge between RNAP sigma 70-dependent operons like hut and the RNAP sigma 54-dependent NTR system. The activation of operons like hut by NAC in response to nitrogen starvation is at least superficially similar to their activation by CAP-cAMP in response to carbon and energy starvation.
Mol Microbiol 1991 Nov
PMID:The role of the NAC protein in the nitrogen regulation of Klebsiella aerogenes. 166 20

Alveolar epithelial lining fluid glutathione (GSH) is markedly decreased in patients with idiopathic pulmonary fibrosis (IPF). Because patients with IPF have exaggerated numbers of fibroblasts in their lower respiratory tract, we hypothesized that GSH can suppress lung fibroblast proliferation. To verify this hypothesis, we examined the ability of GSH to suppress human lung fibroblast (ATCC; HFL-1) proliferation in vitro in the presence of either IPF bronchoalveolar lavage fluid (BAL) or calf serum (CS). Both CS at a concentration of 10% and IPF BAL markedly increased fibroblast proliferation when compared to cells grown without CS or IPF BAL (10% CS = 93 +/- 4%, P less than 0.001; IPF BAL = 47 +/- 4%, P less than 0.001). In the presence of physiologic concentrations of GSH (0 to 500 microM), both CS- and IPF BAL-mediated fibroblast proliferation were markedly reduced, with 500 microM GSH inducing complete inhibition. Interestingly, glutathione disulfide (GSSH) and S-methylglutathione did not suppress proliferation, whereas various sulfhydryl-containing molecules (cysteine, N-acetylcysteine, 2-mercaptoethanol, and low concentrations of dithiothreitol) induced an inhibition of fibroblast proliferation similar to that observed with GSH. Most of the suppressive effect of GSH was mediated at the cell level since incubation of fibroblasts with 500 microM GSH for 1 h completely blocked the ability of the cells to subsequently proliferate in the presence of untreated 10% CS. Treatment of CS with 500 microM GSH for 1 h followed by removal of GSH by molecular sieve chromatography had no detectable effect on fibroblast proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Jul
PMID:Extracellular glutathione suppresses human lung fibroblast proliferation. 236 38

The beta-lyase-dependent bioactivation of S-conjugates of tetrafluoroethylene by subcellular fractions from rat liver and rat kidney was studied. Incubation of both hepatic and renal cytosol with S-(1,2,2,2-tetrafluoroethyl)-l-cysteine (TFE-Cys) resulted in the formation of previously unidentified difluorothionamides, indicating difluorothionoacyl fluoride as the main reactive intermediate derived from the beta-lyase-dependent bioactivation of TFE-Cys. The presence of N-difluorothionoacetyl-S-(1,1,2,2-tetrafluoroethyl)-l-cystei ne (TFE-PMS) and difluoroacetic acid in urine of rats treated with N-acetyl-S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (TFE-NAC) points to a similar mechanism of bioactivation in vivo. When TFE-NAC was incubated with 11,000 X g supernatants of rat kidney and liver in the absence of exogenous acetyl coenzyme A (acetyl-CoA), N-deacetylation and subsequent beta-lyase-dependent activation to difluorothionoacyl fluoride could be observed. Both the N-deacetylation of TFE-NAC and the beta-lyase-dependent activation of TFE-Cys were much faster in rat kidney then in rat liver. When TFE-Cys was incubated with 11,000 X g supernatants of rat kidney and rat liver, formation of TFE-NAC could only be observed in the presence of 2 mM exogenous acetyl-CoA; the initial rate of N-acetylation was 5-fold higher in renal then in hepatic fractions. Under these conditions, formation of TFE-PMS was very low. The low urinary excretion of unchanged TFE-NAC (3-5% of dose) upon administration of TFE-NAC points to a high N-deacetylation/N-acetylation ratio in vivo. Due to a very high turn-over of TFE-NAC/TFE-Cys, the availability of the cofactor for N-acetylation, acetyl-CoA, might be rate limiting in the kidney, resulting in accumulation of TFE-Cys followed by increasing beta-lyase-dependent bioactivation of TFE-Cys to reactive intermediates.
Mol Pharmacol 1989 Oct
PMID:Bioactivation of the cysteine-S-conjugate and mercapturic acid of tetrafluoroethylene to acylating reactive intermediates in the rat: dependence of activation and deactivation activities on acetyl coenzyme A availability. 281 61

The thiol moiety is prone to oxidative free radical formation, which may be important in mediating the toxicity of some thiol-containing compounds. The oxidation of the compounds cysteine, cysteamine, N-acetylcysteine, glutathione, penicillamine, and captopril were studied using ESR and oxygen uptake techniques. Lactoperoxidase, with hydrogen peroxide to provide oxidizing equivalents, was used to initiate the oxidation. The reaction appears to be strongly peroxide dependent, with either exogenous H2O2 or thiol-derived peroxide driving the reaction.
Mol Pharmacol 1987 Apr
PMID:Oxidation of thiol drugs and biochemicals by the lactoperoxidase/hydrogen peroxide system. 303 67

It is known that myocardial ischaemia causes a marked decline of cellular thiol pool and of protein sulphydryl groups content. Reperfusion under these conditions results in oxydative damage which is concomitant with poor recovery of mechanical function. We have evaluated the role of glutathione status in the protection against ischaemic and reperfusion damage by treating the isolated rabbit hearts with N-acetylcysteine (10(-6) M), a sulphydryl group donor. Ischaemic and reperfusion damage was determined in terms of mechanical function, rate of lactate and creatine kinase (CPK) release, mitochondrial function and tissue content of reduced (GSH) and oxidized (GSSG) glutathione and of protein sulphydryl groups (SH). After 60 mins of ischaemia (induced by reducing coronary flow from 24 to 1 ml/min) followed by 30 mins of reperfusion there was an increase of diastolic pressure to 51.6 +/- 3.5 mmHg with only a 22% recovery of systolic pressure, massive CPK release and a deterioration in mitochondrial function. Tissue contents of GSH and of protein SH were severely decreased, while those of GSSG were increased. The GSH/GSSG ratio was reduced from the aerobic value of 50 to 13.4, suggesting that an oxidative stress has occurred. N-acetylcysteine infused for 60 mins before ischaemia determined a 38% increase in tissue content of GSH with no major changes of GSSG or protein SH. The ischaemic-induced decrease of GSH and protein SH was also limited by pretreatment with N-acetylcysteine and there was no accumulation of GSSG after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1988 Jan
PMID:The role of glutathione status in the protection against ischaemic and reperfusion damage: effects of N-acetyl cysteine. 336 79

The hepatotoxicity of N-acetyl-p-aminophenol (acetaminophen, paracetamol) was investigated in hepatocyte cultures obtained from eight different human liver biopsies. Incubation of hepatocytes with paracetamol resulted in a dose- and time-dependent glutathione depletion. Glutathione decreased linearly for 8 h, reaching a minimum after 12 h of exposure. Cytotoxicity, assessed as loss of cellular protein from plates, was observed only when glutathione decreased below 20% for more than 12 h. However, in one donor, cytotoxicity was observed with even a moderate glutathione decrease. Prestimulation of hepatocytes with 1 mM phenobarbital or 2 microM methylcholanthrene for 48 h did not lead to a significant increase of paracetamol toxicity, although the glutathione levels in 3-methylcholanthrene-treated cells were somewhat lower. Several metabolic precursors were examined in vitro for their ability to increase intracellular glutathione and the results showed the following sequence: N-acetylcysteine greater than thioproline greater than cysteine greater than 2-oxo-4-thiazolidine carboxylic acid greater than methionine. However, only N-acetylcysteine, thioproline, and cysteine substantially increased glutathione levels when 1 mM paracetamol was present in the incubation medium and thus prevented its toxicity. N-acetylcysteine elevated glutathione even after 24 h of preexposure to paracetamol. The fact that cell damage did not correlate with glutathione levels in all human cultures suggests that glutathione depletion may not be the only determinant of paracetamol toxicity in human hepatocytes.
Mol Toxicol
PMID:Toxicity of paracetamol in human hepatocytes. Comparison of the protective effects of sulfhydryl compounds acting as glutathione precursors. 350 88

The "energy-rich" thioester, N-acetyl-S-lactoylcysteine, is formed under anaerobic conditions from glyceraldehyde and N-acetylcysteine at ambient temperature in aqueous solutions of sodium phosphate (pH 7.0). The conversion of glyceraldehyde to lactoyl thioester occurs at a rate of about 0.4%/day in reactions with 10 mM glyceraldehyde, 10 mM thiol, and 500 mM sodium phosphate (pH 7.0). Thioester formation proceeds at an estimated efficiency of 76%, since a similar reaction with 12.5 mM thiol yields 50.7% lactate at 6 months from only 66.5% of the glyceraldehyde (or its isomer, dihydroxyacetone). The formation of lactoyl thioester most likely occurs by the phosphate-catalyzed dehydration of glyceraldehyde to give pyruvaldehyde, which combines with thiol to form a hemithioacetal that rearranges to the thioester. A second energy-rich thioester, N-acetyl-S-glyceroylcysteine, is also produced from glyceraldehyde when these reactions are carried out in the presence of oxygen and to a limited extent in the absence of oxygen. In the presence of oxygen the formation of glyceroyl thioester continues until the thiol disappears completely by oxidation. The significance of these reactions to the energetics of the origin of life is discussed.
J Mol Evol 1984
PMID:Nonenzymatic formation of "energy-rich" lactoyl and glyceroyl thioesters from glyceraldehyde and a thiol. 643 34

The ultrastructure of isolated mouse hepatocytes shows good correlation with that of cells from intact liver. Incubation of isolated mouse hepatocytes with 1.0 mM acetaminophen causes a variety of cytoplasmic and cell surface lesions, as well as cell death. The changes are similar or equivalent to those caused by acetaminophen in vivo. The most prominent feature of damage in isolated hepatocytes is bleb formation, which is also seen occasionally in control incubations. The protective compound alpha-mercaptopropionylglycine and the antidote N-acetylcysteine both prevented the acetaminophen-induced changes. It is suggested that the in vivo counterpart to the blebs are endocytic vacuoles which form at cell margins due to the intravascular pressure of the sinusoids. It is suggested that the cell surface changes both in vivo and in isolated hepatocytes are caused by some dysfunction to the microfilament component of the cytoskeleton.
Exp Mol Pathol 1983 Oct
PMID:Ultrastructural effects of acetaminophen in isolated mouse hepatocytes. 661 25


1 2 3 4 5 6 7 8 9 10 Next >>