Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated the effect of lipopolysaccharides (LPS), endotoxins from gram negative bacteria, on sodium-coupled amino acid and phosphate transport by alveolar epithelial type II cells and on their alteration induced by oxidants. Alveolar type II cells were obtained by enzymatic digestion of rat lung and grown for 24 h prior to incubation with LPS and then exposed or not exposed to H2O2 (2.5 mM; 20 min). LPS (10 micrograms/ml, 24 h) induced a significant increase in the Na-dependent component of alanine and phosphate uptake while they decreased Na,K-ATPase activity measured by ouabain-sensitive 86Rb influx. We showed that this stimulatory effect i) was independent from macrophage products since it was not mimicked either by supernatant of LPS-treated alveolar macrophages or by pretreatment with tumor necrosis factor and/or interleukin 1 and ii) was dependent on protein synthesis since it was abolished by protein synthesis inhibitors cycloheximide and actinomycin D. Moreover, LPS blunted H2O2-induced decrease of Na-dependent alanine and phosphate uptake. This protective effect of LPS against H2O2 injury i) was independent of macrophage products, ii) was abolished by cycloheximide, and iii) was not associated with either changes in extracellular H2O2 clearance or catalase and glutathione peroxidase activities. We conclude that, in alveolar type II cells, LPS stimulate sodium-coupled transport by a process involving protein synthesis and partially prevent H2O2-induced decrease of Na-coupled transport without discernible change in antioxidant activities.
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PMID:Lipopolysaccharides stimulate Na-dependent transport in alveolar cells and protect against oxidant injury. 770 77

Human neutrophils, activated by phorbol myristate acetate in the presence of intact red blood cells (RBCs), caused inhibition of the Ca2+ pump ATPase of the RBCs and fragmentation of the enzyme as well as other membrane proteins. Inhibition of the Ca2+ pump ATPase of intact RBCs was directly related to the neutrophil concentration and the time of incubation. Ca2+ pump ATPase activity was partially protected by the addition of exogenous glutathione-glutathione peroxidase, but not by superoxide dismutase. The addition of sodium azide, a potent inhibitor of endogenous RBC catalase, enhanced inhibition of the Ca2+ pump ATPase of intact RBCs. Examination by SDS-polyacrylamide gel electrophoresis of membrane proteins isolated from RBCs preincubated with activated neutrophils showed gross changes in banding patterns as compared to controls. Thus, a significant amount of methemoglobin appeared to be associated with the membrane proteins, and, in general, protein bands appeared to be more diffuse and less defined than proteins in control lanes. In addition, there was an increase in the low molecular weight protein bands. Using a monoclonal antibody to the Ca2+ pump ATPase, it was shown that the 140 kDa band representing the Ca2+ pump ATPase decreased, with concomitant appearance of two low molecular weight bands running at 8.2 and 6.8 kDa in the membrane proteins from RBCs preincubated with activated neutrophils. The data are interpreted to suggest that inhibition of the Ca2+ pump ATPase in intact RBCs under these conditions occurred as a result of: neutrophil-derived superoxide, dismutation of superoxide, to H2O2, diffusion of H2O2 into RBCs, a Fenton type reaction between oxyhemoglobin, and H2O2 producing hydroxyl radical and/or a ferryl radical capable of promoting protein fragmentation of RBC membrane proteins, including the plasma membrane Ca2+ pump ATPase.
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PMID:Inhibition by activated neutrophils of the Ca2+ pump ATPase of intact red blood cells. 775 Jul 90

This study was designed to assess Cyclosporin A (CsA) nephrotoxicity in the rabbit-possibly a more sensitive species than the rat-and to explore the mechanism of this toxicity with special attention to glutathione metabolism disturbances and cytochrome P-450 level in the kidney. CsA given for three days at a daily dose of 50 mg/kg (s.c.) induced nephrotoxicity as assessed by histological abnormalities and by a significant increase in blood urea nitrogen and urinary enzyme activities: N-acetyl-beta-D-glucosaminidase and L-gamma-glutamyl-transferase. This observed renal injury was of the same order as that obtained in the rat. In addition, there was a significant increase in oxidized glutathione content (40%) while reduced glutathione level remained unchanged. Concurrently, there was a significant decrease in renal cortex glutathione reductase (49%) and to a lesser extent in glutathione peroxidase activities (16%) whereas that of glutathione-S-transferase was not modified. A significant increase in renal cortex cytochrome P-450 (3-fold versus controls) was also observed. The mechanism of CsA nephrotoxicity is to be related to a cytochrome P-450 induction. This event could induce the observed impairments in renal glutathione metabolism and Na+K(+)-ATPase activity, via a possible increase in eicosanoid metabolism.
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PMID:Effects of cyclosporin on kidney glutathione metabolism and cytochrome P-450 in the rabbit: possible implication of eicosanoid metabolism. 782 Dec 32

Normal human bronchial epithelial (NHBE) cells are the putative progenitor cells of all types of lung cancer. NHBE cells immortalized by SV40 T-antigen retain many characteristics of the primary cells and are a useful model for investigating the role of oncogenes, tumor suppressor genes, and certain chemical carcinogens in the molecular pathogenesis of lung cancer. In this study, SV40 T-antigen-positive cells (BEAS-2B) were characterized for their metabolic functions and were shown to continue to express epoxide hydrolase, glutathione S-transferase pi, glutathione peroxidase, and catalase. To increase their metabolic activity towards human procarcinogens, human cytochrome P450 1A2 (CYP1A2) was stably expressed by introducing CYP1A2 cDNA into BEAS-2B cells either by infection with a high-titer recombinant retrovirus (pXT-1A2) or by transfection with a CYP1A2 expression vector (pCMV1A2), which produced the cell lines B-1A2 and B-CMV1A2, respectively. Cell lines established with either expression system expressed enzymatically active CYP1A2 protein and were 50- to 400-fold more sensitive to the cytotoxic effect of the carcinogen aflatoxin B1 (AFB1) than the corresponding control cell lines. The cytotoxic effects of AFB1 were paralleled by increased metabolism of AFB1 and enhanced formation of the AFB1-N7 guanine adduct in B-CMV1A2 cells. Cytotoxicity and adduct formation correlated with a significantly higher protein expression of CYP1A2 by the cytomegalovirus promoter-driven plasmid. Since this human epithelial cell line is the precursor cell type of lung cancer, has normal phase II enzymes, and exhibits highly reproducible expression of phase I enzymes, this in vitro model should aid in the evaluation of putative human carcinogens and anticarcinogens.
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PMID:Activation of promutagens in a human bronchial epithelial cell line stably expressing human cytochrome P450 1A2. 791 94

The calcium uptake and ATPase activity were studied using fragmented sarcoplasmic reticulum (FSR) vesicles from normal and selenium (vitamin E)--deficient lambs. The latter group was suffering from white muscle disease (WMD). The calcium uptake of FSR vesicles from muscle of WMD lambs was reduced 10-fold as compared to those from normal lambs. An inverse relationship was found with the calcium uptake ability of the FSR vesicles and the severity of WMD. ATPase activity was nonsignificantly lower in vesicles from WMD lambs. The most active FSR vesicles from both normal and WMD lambs banded at 27% when purified on linear sucrose density gradients. The number of protein bands appearing in acrylamide gels of the purified vesicles appeared to be directly proportional to the severity of WMD. The 75Se cosedimented with the calcium uptake and ATPase activity when FSR vesicles from a lamb injected with 75Se-selenite were subjected to linear sucrose density gradient centrifugation, suggesting that selenium is incorporated into these vesicles. Injection of selenium into WMD lambs resulted in significantly greater calcium uptake activity in vesicles 18 and 38 days later as compared with untreated WMD lambs. Injection of selenium in WMD lambs resulted in a marked decrease in plasma CPK activity and a significant increase of glutathione peroxidase activity in the blood.
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PMID:Calcium uptake and ATPase activity of sarcoplasmic reticulum vesicles isolated from control and selenium deficient lambs. 821 48

Incubation of human red blood cells (RBCs) with t-butyl hydroperoxide (tBHP) resulted in inhibition of the Ca-pump ATPase. This was demonstrated using an assay of the Ca-pump ATPase activity in intact RBCs. In this assay, activity of the Ca-pump ATPase is expressed as the rate constant of the initial loss of ATP in RBCs exposed to Ca and A23187. Pseudo-first-order rate constants (Ca-pump ATPase rate constants) were lower in the presence of tBHP versus controls. Incubation of RBCs with tBHP resulted in both a time- and concentration-dependent inhibition of the Ca-pump ATPase (IC50 approximately 1 mM). Incubation of RBCs with tBHP also resulted in decreased oxyhemoglobin, increased methemoglobin and increased thiobarbituric acid reactive substances (TBARS). GSH levels were significantly lower in the presence of tBHP. GSH fell from a control value of 2.2 mmol/l RBC to 0.46 mmol/l RBC after incubation with 0.25 mM tBHP for 15 min. Both butylated hydroxytoluene and stobadine prevented the formation of TBARS and were partially effective in protecting the Ca-pump ATPase from tBHP-induced inhibition. Dithiothreitol was completely effective in preventing the tBHP-induced formation of TBARS as well as inhibition of the Ca-pump ATPase. However, when added after exposure to tBHP, dithiothreitol was unable to restore Ca-pump ATPase activity completely. An activity of dithiothreitol independent of enzymic thiol group reduction was apparent. In the presence of mercaptosuccinate, a potent inhibitor of glutathione peroxidase, the ability of dithiothreitol to protect the Ca-pump ATPase from tBHP-induced inhibition was abolished. Therefore, protection by dithiothreitol may be afforded by its ability to replenish GSH from oxidized glutathione, thus allowing glutathione peroxidase to metabolize tBHP. These results may be interpreted to suggest that inhibition of the Ca-pump ATPase in intact RBCs occurs as a result of tBHP-induced oxidant stress and subsequent lipid peroxidation which can be prevented by certain antioxidants including butylated hydroxytoluene, stobadine, and thiol-containing compounds such as dithiothreitol. These findings provide further insight into the mode of action of hydroperoxides and certain reactive oxygen species that have been implicated in oxidative stress associated with various pathological conditions. The importance of the GSH/glutathione peroxidase system in metabolizing organic hydroperoxides is also demonstrated.
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PMID:Inhibition of the Ca pump of intact red blood cells by t-butyl hydroperoxide: importance of glutathione peroxidase. 824 Dec 52

Extracorporeal dialysis in uremic subjects produces erythrocyte alterations on energetic and redox metabolism. On this basis, we have tried to verify a fundamental parameter for the integrity of the red blood cell namely the glutathione content both in the oxidized and reduced form. Comparisons were made between two groups of subjects (similar in age, sex and number). One group consisted of uremic subjects undergoing dialysis and the other in healthy controls. As well as a slight increase in reduced glutathione (GSH), an accumulation of oxidized glutathione (GSSG) was found which, in postdialysis patients, reached values up to 3 times higher than in controls. This means a lowering in the ratio GSH/GSSG. There was also a decrease in total Mg(++)-ATPase activity, significantly found in erythrocyte ghosts of postdialysis patients. The hypothesis of a reduced efflux of GSSG as well as an increase in its formation speed (activation of glutathione peroxidase) is taken into consideration.
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PMID:[Extracorporeal hemodialysis: various++ metabolic and erythrocyte-membrane features of uremic subjects]. 832 84

The aim of this study was to better characterize rabbit proximal kidney tubule cells cultured on collagen IV-coated porous inserts, as compared to the same cells seeded in standard plastic wells. Total protein contents in confluent monolayers on permeable membranes were about twofold higher than those measured in confluent cultures in plastic wells. Microscopy examinations suggested that such a difference was probably due to a higher cell density and to an impressive development of the apical brush-border membrane. Moreover, measurement of unidirectional transport of p-aminohippuric acid and tetraethylammonium bromide confirmed the high polarization level of cultures on porous inserts. Results of methyl(alpha-D-[U-14C]glyco)pyranoside uptake suggested that cell phenotype was probably influenced by culture conditions. Analysis of different markers as a function of time in culture showed decreases of alkaline phosphatase (AP), gamma-glutamyltranspeptidase (GGT), and Na(+)-K(+)-ATPase activities as well as increases in LDH, ATP, and glutathione levels, similar to those formerly reported for cells cultured in standard plastic plates. However, comparative data from 6-d-old monolayers have shown that AP, GGT, Na(+)-K(+)-ATPase, glutathione reductase (GRED), and selenium-dependent glutathione peroxidase (Se-GPX) activities were 2.8-, 2.6-, 1.6-, 1.2-, and 2.1-fold, respectively, better preserved on precoated permeable membranes. On the other hand, this paper reports for the first time in the literature that GRED and SE-GPX, two phase II detoxification enzymes, were well maintained in cultures of rabbit proximal kidney tubule cells. Our results show that culturing rabbit proximal kidney tubule cells on collagen IV-coated porous membranes was accompanied by an improvement of both morphological and biochemical properties of the cells.
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PMID:Morphological and biochemical characterization of primary culture of rabbit proximal kidney tubule cells grown on collagen-IV coated Millicell-CM. 935 85

Copper is an essential trace element and has profound influence on cardiac myopathy and heart metabolism. Dietary Cu restriction in rats results in cardiomyopathy, and affects the integrity of the basal lamina of cardiac myocytes and capillaries. Decreased levels of delta subunits of ATP synthetase and nuclear encoded subunits of cytochrome oxidase system have been observed. Alteration in expression of glutathione peroxidase and catalase in heart and liver in Cu deficiency (Cu-) has been noted involving both transcriptional and post transcriptional mechanisms. A short description of two genetically inherited disorders of Cu metabolism, i.e. Wilson's disease and Menkes' disease, and Indian childhood cirrhosis (environmental and/or genetic) have been included to illustrate that advances in the knowledge of Cu cellular transport gives a better understanding of the molecular basis of the pathophysiology of these diseases. Menkes' disease, a human model of defective Cu transport and Cu- has shown many pathological changes, similar to those of heart disease in Cu-. The recent cloning of four genes of putative Cu pumping ATPases (Cu-ATPases) from widely different sources, i.e. two from Enterococcus hirae and one each from Wilson's and Menkes disease patients (which are defective in Cu transport and metabolism), has opened a new chapter in the study of Cu cellular transport and metabolism. The encoded gene products, i.e. Cu-ATPases, show extensive homology and are members of a new class of ATP-driven Cu pumps involved in regulation of cellular Cu. Further, Cu transport by Cop B-ATPase (E. hirae) in membrane vesicles and in isolated rat liver plasma membrane has provided biochemical evidence of its role in ATP-driven Cu transport. In this short review I have critically examined the current evidence of the molecular basis of the pathophysiology of cardiomyopathy in Cu- and, have indicated the possible role of P-type Cu ATPase which may be one of the obligatory factors contributing to cardiomyopathy in experimental animals and probably humans. Experimental verification of this hypothesis will be the aim of future studies.
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PMID:Copper deficiency and heart disease: molecular basis, recent advances and current concepts. 945 22

Cellular redox status and membrane protein activities were analyzed in kidneys from rats with ischemic acute renal failure (ARF). ARF was induced by clamping the left renal artery for 50 min. A parallel group of control animals was processed. In the ischemic group urea plasma levels were statistically increased as compared with the control group. Studies employing whole kidney homogenates revealed that ischemia produces an increment in lipid peroxidation levels and a reduction in glutathione concentration and in superoxide dismutase and glutathione peroxidase activities. Since lipid peroxidation may alter the function of membrane proteins we determined succinate cytochrome c reductase (SuccR), sodium-potassium ATPase (Na-K-ATPase), glucose-6-phosphatase (G-6-Pase) and alkaline phosphatase (ALP) activities in whole renal homogenates. Only G-6-Pase and ALP activities were modified by ischemia. Since ALP is a brush border membrane (BBM) enzyme and BBM is one of the main target structures in ARF, we assessed some parameters of BBM functionality. ALP, gamma-glutamyl transferase (gamma-GT) and 5'-nucleotidase (5'-NT) showed diminished activities in BBM from ischemic kidneys. Ischemia also modified the Vmax of paraaminohippuric acid (PAH) uptake without altering Km. An increment of lipid peroxidation and membrane fluidity in BBM was observed after the treatment. Total membrane proteins and protein recoveries in BBM were similar in both experimental groups. Sialic acid and sulfhydryl levels were similar in BBM from ischemic kidney and control ones. In summary, ARF induced by renal artery clamping for 50 min takes place with a significant increase in urea plasma levels. A decrease in the antioxidant defense system is detected. This induces lipid peroxidation in whole renal tissue, which may justify the diminished activities of some membrane enzymes such as G-6-Pase and ALP. A specific analysis of BBM function reveals a significant increment of lipid peroxidation which may be the cause of an increased membrane fluidity. This latter parameter might be, at least in part, responsible for the damaged function of apical ALP, 5'-NT, gamma-GT and PAH carrier.
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PMID:Impairment of cellular redox status and membrane protein activities in kidneys from rats with ischemic acute renal failure. 968 97


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