Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report compares the effects of adrenalectomy and thyroidectomy, with and without hormone replacement, on loss of contractile protein ATPase activities. The rationale for this study was derived from the similarities in their intracellular receptors, mechanisms of action, and the large number of proteins regulated by both hormones. Rats were adrenalectomized, thyroidectomized, or both, and were subsequently treated for 6 weeks with hydrocortisone, triiodothyronine, or saline. Sham-operated rats were given saline for the same period of time. Six weeks of adrenal insufficiency resulted in diminished enzymatic activity of myofibrillar, Ca(2+)-activated myosin ATPase, and actin-activated myosin ATPase fractions. Treatment with hydrocortisone prevented the decline in enzymatic activity due to adrenalectomy. Likewise, thyroidectomy caused a loss of enzymatic activity which was prevented by treatment with triiodothyronine. The full deleterious effect of combined ablation could be partially prevented by treatment with either hydrocortisone or triiodothyronine, but the latter was most effective. The results suggest that hydrocortisone and triiodothyronine each had significant positive effects in the presence of the other, but not in its absence, on the activity of myofibrillar Ca(2+)-dependent Mg-ATPase and Ca(2+)-activated myosin ATPase. The effects of these two hormones on actin-activated myosin ATPase activity were more independent of each other. We conclude that the actions of thyroid and glucocorticoid hormones on the heart are interrelated and that optimum myocardial function results from their combined action.
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PMID:Myocardial contractile protein ATPase activities in adrenalectomized and thyroidectomized rats. 148 85

In view of the known effects of cortisol and related compounds on sodium balance, we examined leucocyte 22Na+ efflux in patients with adrenocortical insufficiency. The ouabain-sensitive 22Na+ efflux rate constant, which reflects sodium pump activity, was lowered in secondary hypoadrenalism (mean 1.95 +/- SD 0.25 vs 2.33 +/- 0.45 h-1, P less than 0.002, n = 6). Patients with hypoadrenalism also had higher intracellular sodium content (mean 34.9 +/- SD 3.5 vs 27.8 +/- 9.5 mmol/kg dry weight, P less than 0.008) and lower intracellular potassium to sodium ratios (mean 9.7 +/- SD 0.7 vs 12.9 +/- 3.6, P less than 0.001). These defects in cellular sodium balance were corrected following replacement therapy with cortisol, prednisolone or dexamethasone. In-vitro incubation of normal leucocytes with 5-20 nmol/l dexamethasone led to an increase in the Na+/K+-ATPase activity. The effect of cortisol and related compounds on the distribution of sodium between intra- and extra-cellular fluid may be mediated by their action on the sodium pump.
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PMID:The human leucocyte sodium pump in adrenocortical insufficiency. 366 31

X-linked adrenoleucodystrophy is a disorder occurring in different clinical forms, characterized by adrenal, gonadal and nervous system dysfunction. The basis of the illness is a derangement of the peroxisomal system necessary to oxidize very long-chain fatty acids that accumulate in various tissues. The diagnosis relies on clinical signs and symptoms and on biochemical findings. The six reported cases presented idiopathic adrenal insufficiency. We measured the lipid composition of red blood cell (RBC) ghosts of patients and control subjects. The distribution of phosphorus among phospholipid classes was unaffected; we could not demonstrate any differences between the fatty acid patterns of RBC membrane, either in total lipid extracts or in separated lipid classes. However, we found an increase in total lipid (both phospholipid and cholesterol), in membrane viscosity and in the Na+/K(+)-dependent ATPase. Therefore, we report four main findings on ghosts in adrenoleucodystrophy patients: (a) very long-chain fatty acids do not accumulate; (b) the lipid-protein ratio increases; (c) fluidity decreases; and (d) the activity of ATPase increases. The last finding is proposed as a possible biochemical marker of the illness. We conclude that adrenoleucodystrophy affects deeply RBC membranes.
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PMID:Red blood cell ghosts are affected by adrenoleucodystrophy. 891 66

The autoimmune polyendocrine syndrome type II (APS-II) is characterized by the association of autoimmune Addison's disease with thyroid autoimmune diseases or type-1 diabetes mellitus. 21-Hydroxylase autoantibodies enable the accurate diagnosis of autoimmune Addison's disease and, in patients with other endocrine autoimmune diseases, identify subjects at high risk for clinical adrenal insufficiency. 17 alpha-Hydroxylase (17OH) and side-chain-cleavage enzyme (P450scc) are target autoantigens of steroid-cell autoantibodies, and in women with Addison's disease, 17OH autoantibodies and P450scc autoantibodies are markers of increased risk for premature ovarian failure. Thyroperoxidase autoantibodies, thyroglobulin autoantibodies, H+/K(+)-ATPase autoantibodies, and GAD65 autoantibodies are frequently detected in patients with isolated Addison's or APS-II. Screening for other organ-specific autoimmune diseases should be performed in every patient with at least one major disease component of APS-II.
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PMID:Autoantibodies in autoimmune polyendocrine syndrome type II. 1209 56

X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1(-) mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1(-) mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1(-) mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALD.
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PMID:Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy. 2360 18