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

Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.
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PMID:The effects of lithium therapy on thyroid and thyrotropin-releasing hormone. 982 58

The molecular recognition hypothesis for peptides is that binding sites of ligands and their receptors are encoded by short, complementary segments of DNA. A corollary hypothesis for nonpeptide ligands posited here is that peptide replicas may be encoded by the DNA segment complementary to the receptor binding sites for nonpeptides. This corollary was tested for digitalis. a family of cardiotonic and natriuretic steroids including ouabain. A hexapeptide (ouabain-like peptide, OLP) complementary to a ouabain binding site on sodium potassium dependent adenosine triphosphatase (Na+ K+ ATPase) exhibited activity in a digitalis bioassay. Antisera to the complementary peptide (OLP) stained the neurohypophysis in an immunocytochemical procedure. The complementary peptide was found to share an identical 4-amino acid region with the 39-amino acid glycopeptide moiety of the vasopressin-neurophysin precursor. This glycopeptide was isolated from pituitary extracts; it exhibited digitalis-like activity in the submicromolar range and cross-reacted with complementary peptide antibodies. Another digitalis-like substance with high activity also was detected in the extracts. These results demonstrate that the vasopressin-neurophysin glycopeptide has digitalis-like activity. Moreover, the findings are consistent with the hypothesis that peptide mimetics of nonpeptides are encoded in the genome.
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PMID:A molecular recognition hypothesis for nonpeptides: Na+ K+ ATPase and endogenous digitalis-like peptides. 1035 21

Clofibrate is a peroxisome proliferator that can cause hepatic cancer in rodents. It has been suggested that oxidative damage is involved in this hepatocarcinogenesis, although the data are conflicting. We confirmed that clofibrate causes oxidative damage in nuclei from the livers of mice treated with this substance, measured both as protein carbonyls and levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA. In addition, clofibrate also affects mitochondria, causing elevated levels of carbonyls and 8-OHdG, increased state 4 respiration and decreased adenosine triphosphatase (ATPase) activity. No evidence for clofibrate-induced lipid peroxidation in mitochondria was obtained. We propose that mitochondria may be a major target of injury and a source of oxidative stress in clofibrate-treated animals.
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PMID:Mitochondrial damage by the "pro-oxidant" peroxisomal proliferator clofibrate. 1056 42

The T8993G mutation in the mitochondrial DNA adenosine triphosphatase 6 gene represents an important cause of maternally inherited Leigh's syndrome. Reported are the clinical findings and mutational loads in three Portuguese T8993G pedigrees. Polymerase chain reaction-restriction fragment length polymorphism analyses demonstrated the T8993G mutation in a high percentage of tissues from all patients (97% +/- 2.3%), but it was less abundant in the blood from 14 maternal relatives. The disease progressed severely in the probands but did not have the fatal course reported by others. To test whether this prolonged course was related to the presence of a specific, disease-associated haplogroup the origin of the mutational event in Portugal was traced. Haplotype investigation revealed an independent occurrence of the mutation in the three probands. These analyses represent the first molecular characterization of Portuguese patients with Leigh's syndrome.
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PMID:Clinical and molecular studies in three Portuguese mtDNA T8993G families. 1066 2

The effect of exposure to sublethal concentrations of the organophosphate pesticide, quinalphos (1.12, 0.22 mg/l) on biochemical parameters of muscle and enzyme activities in brain, liver and kidney of the Indian major carp, Labeo rohita was studied after 15, 30 and 45 days. The muscle protein and RNA levels decreased whereas DNA levels and acid phosphatase were elevated. Similarly, alkaline phosphatase was depleted. The brain acetyl cholinesterase activity was decreased most (-75.43%) in 1.12 mg/l concentration over a period of 45 days. Lactic dehydrogenase levels in brain and liver were elevated whereas in the kidney they were inhibited. Succinic dehydrogenase and adenosine triphosphatase activities were depleted in brain, liver and kidney. The effects have been discussed for different organ tissues in relation to the pesticide.
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PMID:Chronic toxic effects of quinalphos on some biochemical parameters in Labeo rohita (Ham.). 1071 64

Of 100 patients with the clinical diagnosis of Leigh syndrome, 21 were found to have specific enzyme defects: 15 involving cytochrome c oxidase (COX); 4, pyruvate dehydrogenase complex (PDHC); one, complex I (reduced nicotinamide adenine dinucleotide [NADH]-coenzyme Q reductase) and one, complex II (succinate-ubiquinone reductase) deficiencies. In addition to the most common form of COX deficiency, mtDNA mutations in the adenosine triphosphatase (ATPase) 6 coding region were also commonly seen. Eighteen patients (18%) had mtDNA mutations at nucleotide position (np) 8993 or 9176. The mutated DNAs were present in a heteroplasmic state, comprising more than 90% of the DNA in muscle and/or blood samples from all patients. Patients with the T-to-G mutation at np 8993 usually had early onset of the disease with rapid progression, showing the typical clinical features of Leigh syndrome. On the other hand, those with the T-to-C 8993 mutation showed a milder and more chronic course. Patients with the mutation at np 9176 showed variable courses. Phylogenetic analysis of mtDNA D-loop sequences for the patients with the ATPase 6 mutations and normal Japanese subjects revealed that a T-to-G/C mutation at np 8993 and a T-to-C mutation at np 9176 occurred many times independently in the Japanese population.
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PMID:Mitochondrial DNA mutations in Leigh syndrome and their phylogenetic implications. 1072 66

To study the histochemical alterations of hookworm L3 administered in a challenge dose to mice vaccinated previously with the larvae. Male Kunming strain mice vaccinated subcutaneously with 500 living Ancylostoma caninum L3 once every 2 weeks for a total of three immunizations before a final challenge with 500 L3 one week after the final immunization. The abdominal skin with underlying subcutaneous tissue and muscle were removed from the site of percutaneous challenge entry (from 2-3 mice), and fixed in absolute alcohol, cold acetone and 10% neutralized formalin. The tissue sections containing the L3 from the challenge dose were then stained histochemically of glycogen, RNA, DNA alkaline protein, acid mucopolysaccharide, collagen, reticulin, alkaline phosphatase (AKP) and adenosine triphosphatase (ATPase). Skin samples from non-immunized mice that were also subcutaneously inoculated with the L3 served as negative control. The L3 identified in cutaneous sections from vaccinated mice at 6-72 hours post-challenge exhibited reductions in parasite glycogen, alkaline protein, RNA and DNA, as well as reductions in acid mucopolysaccharide, collagen and reticulin contents in the parasite cuticle. There were also reduced enzyme AKP and ATPase activities. In contrast L3, identified in sections from non-immunized mice exhibited a normal histochemical appearance, as did some L3 who survived in vaccinated mice at 7-14 days post-challenge. Vaccination results in hookworm L3 damage which is manifested by reduced histochemical staining for the challenge inoculum of parasites. There is also reduced hydrolytic enzyme activity. The observed changes could reflect either host-mediated parasite structural damage and disintegration or possibly anti-metabolic properties of the host immune response.
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PMID:Histochemical alterations of infective third-stage hookworm larvae (L3) in vaccinated mice. 1077 9

The SpoIIIE protein of Bacillus subtilis is required for chromosome segregation during spore formation. The COOH-terminal cytoplasmic part of SpoIIIE was shown to be a DNA-dependent adenosine triphosphatase (ATPase) capable of tracking along DNA in the presence of ATP, and the NH(2)-terminal part of the protein was found to mediate its localization to the division septum. Thus, during sporulation, SpoIIIE appears to act as a DNA pump that actively moves one of the replicated pair of chromosomes into the prespore. The presence of SpoIIIE homologs in a broad range of bacteria suggests that this mechanism for active transport of DNA may be widespread.
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PMID:Role of Bacillus subtilis SpoIIIE in DNA transport across the mother cell-prespore division septum. 1106 34

Vascular remodeling is a key feature of many pathologic states, including atherosclerosis, or hypertension. Vascular smooth muscle cells participate in determining the vessel structure by several mechanisms such as cell migration, cell growth, or cell death (necrosis or apoptosis). Here we report that thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ -adenosine triphosphatase (ATPase), is able to induce apoptosis in human vascular smooth muscle cells (HVSMCs). Apoptosis was assessed by three different methods: differential chromatin binding dye staining. cytoplasmic histone-associated DNA fragments detection by enzyme-linked immunosorbent assay (ELISA) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). When HVSMCs were treated for 1 h with thapsigargin (100 nM-10 microM), there was a concentration-dependent increase in both parameters 24 h after the thapsigargin pulse. When a time-course experiment was performed, both parameters were significantly enhanced from 3 to 6 h after the exposure to thapsigargin. We conclude that thapsigargin promotes apoptosis in HVSMCs, providing a useful tool for the study of programmed cell death in human vascular smooth muscle.
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PMID:Thapsigargin induces apoptosis in cultured human aortic smooth muscle cells. 1106 29

Leigh syndrome is a progressive neurodegenerative disease frequently associated with mitochondrial abnormalities. The mitochondrial DNA T9176C mutation in the adenosine triphosphatase 6 gene has recently been described as a cause of Leigh syndrome. Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods. Two unrelated patients were found to be homoplasmic for this mutation in blood. Both patients had similar clinical and biochemical features. They had first presented acutely at 3 and 5 years, respectively, with ataxia and slurred speech. Magnetic resonance imaging changes were consistent with Leigh syndrome, and the cerebrospinal fluid lactate was elevated. They have both had relatively stable disease since the time of diagnosis. The mother of one of the children had presented at age 29 years with sudden onset of ataxia, headache, and blurred vision. She was heteroplasmic for the T9176C mutation. The T1976C is an important cause of Leigh syndrome especially in the subgroup of patients with more stable disease and normal respiratory chain enzyme analysis.
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PMID:Mitochondrial DNA point mutation T9176C in Leigh syndrome. 1119 6


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