Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the phospholipase-stimulating and immunosuppressive properties of the riminophenazine anti-mycobacterial agent clofazimine and its experimental analogue, B669, has been investigated in vitro. At concentrations of 0.6 microM and upwards, both riminophenazines, particularly B669, caused dose-related inhibition of mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leucocytes (MNL), while in short-term assays both agents increased the release of lysophosphatidylcholine (LPC) and arachidonic acid from these cells. Arachidonate per se at a concentration of 20 microM did not affect mitogen-activated lymphocyte proliferation, while cyclooxygenase and 5'-lipoxygenase inhibitors, as well as water- and lipid-soluble oxidant-scavengers and anti-oxidant enzymes, failed to protect the cells against the anti-proliferative effects of clofazimine and B669. However, LPC caused dose-related inhibition of lymphocyte proliferation. Moreover, co-incubation of NML with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase, protected the cells against clofazimine and B669, as well as against LPC. Na+, K(+)-adenosine triphosphatase was identified as the primary target of riminophenazine/LPC-mediated inhibition of lymphocyte proliferation. Excessive release of anti-proliferative lysophospholipids during clofazimine or B669 treatment of mitogen- or antigen-activated lymphocytes is the probable biochemical mechanism of the immunosuppressive activity of these agents.
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PMID:Clofazimine and B669 inhibit the proliferative responses and Na+, K(+)-adenosine triphosphatase activity of human lymphocytes by a lysophospholipid-dependent mechanism. 826 51

The effect of vitamin E (VE) or diazepam (DZ) pretreatment on some carbohydrate metabolic aspects in the brains of stressed rats was studied. DZ and VE were given i.p. at doses of 5 mg/kg body wt for 6 days prior to subjecting the animals to single swimming stress (SSS). Pretreatment of the rats with DZ or VE diminished the stress-induced increases in plasma corticosterone and glucose levels and reversed the decrease due to stress on brain ATP, glucose, glycogen and pyruvate contents. The increase in brain ADP and lactate was brought back to levels which approached the pre-stressed values. Moreover, DZ and VE pretreatments helped in attenuating the stress-induced alteration in brain mitochondrial and cytosolic hexokinase as well as sodium, potassium adenosine triphosphatase (Na+,K(+)-ATPase) activities. The change in these metabolic parameters produced by VE pre-treatment was less than that exhibited by DZ. The effects of VE were explained in light of its antioxidant property in preventing the free radical production and lipid peroxide formation which are important factors in the pathogenesis of stress.
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PMID:Effect of pretreatment with vitamin E or diazepam on brain metabolism of stressed rats. 839 75

We have investigated the effects of cyclosporin A (CsA, 3-50 ng/ml) in combination with the riminophenazine agents clofazimine and B669 (60-500 ng/ml) on the mitogen- and alloantigen-activated proliferative responses of human mononuclear leukocytes (MNL), as well as on the phospholipase A2 and Na+, K+- adenosine triphosphatase activities of these cells. When used in combination these agents caused inhibition of the proliferative responses of both mitogen- and alloantigen-activated MNL which was at least additive. Combinations of CsA with the riminophenazines also caused augmentative activation of PLA2 and inhibition of Na+, K+-ATPase. The inhibitory effects of these agents, both individually and in combination, on the Na+, K+-ATPase and proliferative responses of MNL were neutralized by the membrane-stabilizing, lysophospholipid complex-forming agent alpha-tocopherol (vitamin E, 20 microgram/ml). These observations suggest that combinations of CsA with riminophenazines cause interactive enhancement of the activity of PLA2 in MNL leading to lysophospholipid-mediated inactivation of Na+, K+-ATPase and consequent inhibition of the proliferative responses of these cells. In the therapeutic setting combinations of these agents may enable reduction in the dose of CsA required to achieve meaningful immunosuppression with a consequent decrease in the risk of chemotherapy-related organ toxicity.
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PMID:Augmentative inhibition of lymphocyte proliferation by cyclosporin A combined with the riminophenazine compounds clofazimine and B669. 884 96

Mercury intoxication has been associated with male reproductive toxicity in experimental animals and mercury may have the potential to produce adverse effects on fertility in men. Vitamin E may protect against toxic effects of mercury in the liver and other tissues. To investigate the protective role of vitamin E against mercuric chloride toxicity for the testis, epididymis, and vas deferens of adult male mice, animals were treated with either mercuric chloride 1.25 mg/kg/day, vitamin E 2 mg/kg/kg, or a combination of the two treatments. Control animals were treated with water. Treatments were administered by daily gavage for 45 days. An additional group of animals treated with mercuric chloride were permitted to recover for 45 days after mercuric chloride treatments. Parameters studied included serum testosterone, epididymal sperm count, motility, and morphology, epididymal and vas deferens adenosine triphosphatase (ATPase), phosphorylase, sialic acid, glycogen and protein, testicular succinate dehydrogenase (SDH), phosphatases, cholesterol, ascorbic acid, and glutathione. Fertility was evaluated by sperm positive vaginal smears after overnight cohabitation with a female. Mercuric chloride produced a reduction in epididymal sperm count, sperm motility, and sperm viability, and there were no sperm-positive smears in this group. Biochemical tests from the male reproductive organs were also altered by mercuric chloride treatment. Coadministration of vitamin E with mercuric chloride prevented the changes in sperm and biochemical parameters and was associated with control rates of sperm positive smears after cohabitation. Animals given vitamin E with mercuric chloride also had lower concentrations of mercury in the testis, epididimyis, and vas deferens. Permitting animals to recover for 45 days after mercuric chloride treatment resulted in partial recovery of sperm and biochemical parameters. Vitamin E cotreatment has a protective role against mercury-induced male reproductive toxicity.
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PMID:Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice. 1173 24

Membrane injury facilitated the fixation of calcium oxalate crystals and subsequent growth into kidney stones. Oxalate-induced membrane injury was mediated by lipid peroxidation reaction through the generation of oxygen free radicals. In urolithic rat kidney or oxalate exposed cultured cells, both superoxide anion and hydroxyl radicals were generated in excess, causing cellular injury. In hyperoxaluric rat kidney, both superoxide and H2O2-generating enzymes such as glycolic acid oxidase (GAO) and xanthine oxidase (XO) were increased, and hydroxyl radical and transition metal ions, iron, and copper were accumulated. The lipid peroxidation products, thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and diene conjugates were excessively released in tissues of urolithic rats and in plasma of rats as well as stone patients. The accumulation of these products was concomitant with the decrease in the antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glucose-6 phosphate dehydrogenase (G6PD) as well as radical scavengers, vitamin E, ascorbic acid, reduced glutathione (GSH), and protein thiol. All the above parameters were decreased in urolithic condition, irrespective of the agents used for the induction of urolithiasis. Oxalate binding activity and calcium oxalate crystal deposition were markedly pronounced, along with decreased adenosine triphosphatase (ATPase) activity. Lipid peroxidation positively correlated with cellular oxalate, oxalate binding, gamma-glutamyl carboxylase, and calcium level and negatively correlated with GSH, vitamin E. ascorbic acid, and total protein thiol. Antioxidant therapy to urolithic rats with vitamin E, glutathione monoester, methionine, lipoic acid, or fish oil normalised the cellular antioxidant system, enzymes and scavengers, and interrupted membrane lipid and protein peroxidation reaction, ATPase inactivation, and its associated calcium accumulation. Antioxidant therapy prevented calcium oxalate precipitation in the rat kidney and reduced oxalate excretion in stone patients. Similarly, calcium oxalate crystal deposition in vitro to urothelium was prevented by free radical scavengers such as phytic acid and mannitol by protecting the membrane from free radical-mediated damage. All these observations were suggestive of the active involvement of free radical-mediated lipid peroxidation-induced membrane damage in the pathogenesis of calcium oxalate crystal deposition and retention.
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PMID:Calcium oxalate stone disease: role of lipid peroxidation and antioxidants. 1194 24

Present investigation was planned to evaluate the therapeutic effectiveness of chelating agents against vanadium intoxication on blood and reproductive organs of rats. Male and female albino rats were injected vanadyl sulphate (7.5 mg/kg, po, for 21 days, 5 days in a week). Chelating agents tiron (T) alone and in combination with lipoic acid (LA), vitamin E (vit E) and selenium (Se) were given for 2 days/week. With the administration of vanadyl sulphate to rats fructose level in seminal vesicles was significantly (P< or =0.05) declined. The activities of alkaline phosphatase and adenosine triphosphatase were also decreased, whereas glycogen content and acid phosphatase activity increased in testis, seminal vesicles, ovaries and uterus after toxicant exposure. Significant changes in serum transaminases, serum alkaline phosphatase and lactate dehydrogenase were recouped by chelation therapy. Lipid peroxidation, reduced glutathione level and triglycerides levels altered significantly after exposure to vanadium in rats. The ultrastructural damage in spermatogenic stages in treated animals showed recovery pattern after therapy. Co-treatment with antioxidants restored these activities. The most effective combination was tiron + selenium followed by tiron + vitamin E, and tiron + lipoic acid.
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PMID:Chelation therapy and vanadium: effect on reproductive organs in rats. 1758 85

The present investigation was an attempt to evaluate the effect of aflatoxin on biochemical and histopathological changes in the epididymis of mice and its possible amelioration on pre-treatment with vitamin E. Adult male albino mice were orally administered with 25 and 50 mg of aflatoxin/animal/day (750 and 1500 mg/kg body weight) for 45 days. Epididymis was isolated and processed for biochemical analysis. As compared with the control, absolute and relative epididymal weights were significantly reduced in aflatoxin-treated mice. Aflatoxin treatment caused significant, dose-dependent reduction in protein and sialic acid contents in caput and cauda epididymis than that of vehicle control. While activities of succinic dehydrogenase and adenosine triphosphatase were significantly reduced, acid phosphatase activity was significantly higher in caput and cauda epididymis of aflatoxin-treated mice than that of vehicle control. Pyknosis of epithelial cell nuclei, disorganization of epithelium, clumping of stereocilia and lumen devoid of sperms in caput and cauda epididymis were observed. Thus, pre-treatment with vitamin E (2 mg/0.2 mL olive oil/ animal/day) significantly ameliorated aflatoxin-induced changes, measured by biochemical and histopathological parameters.
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PMID:Vitamin E ameliorates aflatoxin-induced alterations in the epididymis of mice. 1864 52

Arsenic is an ubiquitous and well-documented carcinogenic metalloid. The most common source of arsenic is drinking water. The mechanism of arsenic toxicity in a cell has historically been centered around its inhibitory effects on cellular respiration and mitochondrial injury. Ascorbic acid, a low molecular weight, water-soluble antioxidant, improves the reduced glutathione (GSH) status by recycling oxidized glutathione. Ascorbic acid can improve mitochondrial function by improving the thiol status; thereby preventing reactive oxygen species- mediated damage to liver as well as kidney. Ascorbic acid has been shown to protect membrane and other cellular compartments by regenerating vitamin E. Therefore, ascorbic acid seems to be a suitable protective factor against arsenic toxicity. Present reports describe the effect of ascorbic acid on oxidative phosphorylation, adenosine triphosphatase (ATPase), succinic dehydrogenase, caspase-3 and apoptosis in the liver of rats treated with arsenic trioxide (As(III)). Ultrastructural changes in the mitochondria have also been reported. We show that cotreatments with ascorbic acid and As(III) improve mitochondrial structure and function. We attribute these improvements mainly to antioxidative role of ascorbic acid. Apoptosis was restricted due to caspase-3 inhibition. Ascorbic acid could protect DNA from the attack of reactive oxygen species generated by As(III). Consequently its events led to improved ADP:O ratio, normalized ATPase activity and restored the activity of succinic dehydrogenase. Overall, results support the protective role of ascorbic acid against As( III)-induced liver injury.
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PMID:Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat. 2035 60

In the present investigation, we have used adenosine triphosphatase (ATPase) activity as biochemical test of toxic action of lindane that was explained by lipid peroxidation model. Study was also undertaken to ascertain the potential protective role of alpha-lipoic acid (ALA) and vitamin E on the same parameters. Highly acute dose of lindane, i.e., 40 mg/kg bw for 18 h exposure, was used for creating lesions in brain. Lipid peroxidation was measured in terms of glutathione peroxidase and thio barbituric acid-reacting substances (TBARS). Various brain regions under investigation were cerebellum and pons-medulla oblongata. Healthy, male, Swiss mice (7-8 weeks old) were allocated into four groups. First group was control, second group was treated with lindane, third group was treated purely with antioxidants, and fourth group received both antioxidants and lindane treatment. Results revealed the significant difference (at 1% and 5% in all groups) in all studied parameters from control. Increased TBARS level in second group suggests that lindane enhances the production of free radicals in studied brain regions. Antioxidants under test are efficient remedy for neurotoxicity caused by lindane. We conclude that lindane manifests toxic effects on brain ATPase and enhances lipid peroxidation. ALA and vitamin E in combination may provide protection against lindane-induced acute toxicity.
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PMID:Inhibition of lindane-induced toxicity using alpha-lipoic acid and vitamin E in the brain of Mus musculus. 2049 Jun 10

In the present investigation neurotoxic effects of lindane and the protective potential of a combination of antioxidants against lindane-induced toxicity were evaluated in Swiss mice. The investigation was carried out on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and adenosine triphosphatase (ATPase) activities of the cerebellum and pons-medulla oblongata. Healthy mice, 7-8 weeks old were administered acute dose of lindane (40 mg/kg b.w.), antioxidants, both lindane and antioxidants, and vehicle in four separate groups, subcutaneously. Resveratrol (Res), ascorbic acid (C), alpha-lipoic acid (ALA) and vitamin E (E) were used in the combination for neuroprotection at the concentration of 5 mg/kg b.w., 50 mg/kg b.w., 20 mg/kg b.w. and 50 mg/kg b.w. respectively. Enzymatic activities were used as biochemical marker for manifestation of lindane-induced acute toxicity. Protective effects of antioxidants were also evaluated using the same parameters. Treatment of lindane to normal control animals resulted in a significant decrease in AChE, BChE and ATPase levels in crude homogenates of cerebellum and pons-medulla. Antioxidants treatment significantly increased the levels of enzymes. Critical difference (CD) of AChE, BChE and ATPase levels in various groups was found significant at 1% in cerebellum and pons-medulla both (i.e. P<0.01).
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PMID:Augmentation of cholinesterases and ATPase activities in the cerebellum and pons-medulla oblongata, by a combination of antioxidants (resveratrol, ascorbic acid, alpha-lipoic acid and vitamin E), in acutely lindane intoxicated mice. 2066 16


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