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)

In a recent study in acutely parathyroidectomized, fasted rats, infused with parathyroid hormone (PTH), superimposition of euglycemic hyperinsulinemia within the physiologic range completely reversed the decline in tubular reabsorption of Pi (TRPi) induced by PTH. As an extension of these observations on insulin as a counterregulator of Pi homeostatis, the present results demonstrated that similar insulin administration prevented a decrease in TRPi when PTH infusion was superimposed. This was, moreover, observed in the fed state and at doses of insulin which did not stimulate renal cortical Na-K-ATPase activity. Subsequent studies addressed the role of insulin in a PTH-independent phosphaturic state, namely that induced by Pi loading. Under such conditions and while the resultant hypocalcemia of hyperphosphatemia was circumvented by the addition of calcium to the infusate, insulin substantially increased the renal tubular reabsorptive capacity for Pi, thereby demonstrating an antiphosphaturic action of insulin independent of PTH. Furthermore, when increased filtered loads of Pi and PTH administration were combined during insulin infusion, TRPi was greater than when PTH was administered alone during similar insulin infusion. When calcium infusion did not accompany Pi loading with a resultant fall in serum calcium, euglycemic hyperinsulinemia did not affect TRPi, indicating abolition of the antiphosphaturic action of insulin by hypocalcemia.
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PMID:Effects of physiologic hyperinsulinemia on renal phosphate handling in the rat: a role for calcium. 269 27

Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (associated with dietary phosphate restriction in the latter case) on the apical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutamyl-transferase and alkaline-phosphatase, and one BBM Na-phosphate cotransporter (NaPi-2) were studied in rats after a six week period. Changes in activity and mRNA abundance of the BBM enzymes and in NaPi-2 protein and mRNA abundance were compared with changes in the distal markers of Na,K-ATPase activity and epidermal growth factor (EGF) production. The activity, but not the mRNA of BBM enzymes, was moderately reduced by the 70% Nx. Both the mRNA and activity of gamma glutamyl-transferase and alkaline-phosphatase were decreased in the 80% Nx, and the NaPi-2 mRNA, protein and Na,K-ATPase activities were also reduced. These effects (except for 5'nucleotidase and Na,K-ATPase) were partly reversed by phosphate restriction. Overproduction of EGF occurred after the 70% Nx, was blunted in the 80% Nx, and then partially restored by phosphate restriction. Aggravation of tubular alteration was associated with enhanced renal hyperplasia (increased DNA mass), reduced GFR and hyperphosphatemia, and high PTH levels, but reduced cAMP excretion. Improvement following phosphate restriction was associated with reduced hyperplasia and lowering of phosphatemia and PTH levels. These data demonstrate that Nx selectively affected BBM function through transcriptional changes that were partially reversed by phosphate restriction. Regulatory factors involved in these changes may include intracellular phosphate content and growth factors, but not the PTH effects that are impaired in chronic renal failure.
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PMID:Subtotal nephrectomy alters tubular function: effect of phosphorus restriction. 940

The discovery that two recently identified molecules, klotho and fibroblast growth factor 23 (FGF23), played an important role in calcium, phosphate, and vitamin D metabolism has transformed our traditional physiological view in which bone and mineral homeostasis was mainly regulated by parathyroid hormone, vitamin D, and calcitonin, according to mineral body needs. FGF23 is a 251-amino acid secreted protein produced by osteoblasts and osteocytes in bone following the stimulation by phosphate and vitamin D or the inhibition by dentin matrix protein 1. Originally isolated from tumoral cells of patients with tumor-induced osteomalacia and hypophosphatemia, FGF23 inhibits phosphate reabsorption in renal proximal tubular cells and 1alpha-hydroxylase activity, resulting in decreased synthesis of calcitriol. To exert these actions, FGF23 requires the conversion, by klotho, of the canonical FGF receptor 1 (IIIc) in a specific high affinity FGF23 receptor. On the other hand, klotho is a putative antiaging gene identified in 1997 when a particular mouse strain, created by random insertion mutagenesis, was found to be short-lived and displayed premature atherosclerosis, osteopenia, skin atrophy, pulmonary emphysema, hyperphosphatemia, hypercalcemia, and high serum calcitriol levels. The gene of klotho encodes a 1012-amino acid cell-surface protein with a short cytoplasmic tail and an extracellular domain that consists in tandem duplicated copies of a beta-glucuronidase-like sequence, which can be released into the circulation as soluble forms after being cleaved by metalloproteinases such as ADAM10 and ADAM17. By modulating FGF23 action, klotho regulates urinary phosphate excretion and calcitriol synthesis. By virtue of its beta-glucuronidase activity, klotho deglycosylates the calcium channel TRPV5 (transient receptor potential vallinoid-5) and regulates urinary calcium excretion. klotho also binds to Na(+),K(+)-ATPase in parathyroid cells and regulates calcium-stimulated PTH secretion. Finally, klotho extends life span via several mechanisms, including the reduction of calcitriol synthesis, serum calcium, and phosphorus levels; the induction of insulin resistance; and by increasing the resistance to oxidative stress.
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PMID:Klotho gene, phosphocalcic metabolism, and survival in dialysis. 1912 71

Klotho is a protein of significant importance for mineral homeostasis. It helps to increase parathyroid hormone (PTH) secretion and in the trafficking of Na+/K+-ATPase to the cell membrane; however, it is also a cofactor for fibroblast growth factor (FGF)-23 to interact with its receptor, FGFR1 IIIC, resulting in decreased PTH secretion. Studies on the regulation of parathyroid klotho expression in uremia have provided varying results. To help resolve this, we measured klotho expression in the parathyroid and its response to severe uremia, hyperphosphatemia, and calcitriol treatment in the 5/6 nephrectomy rat model of secondary hyperparathyroidism. Parathyroid klotho gene expression and protein were significantly increased in severely uremic hyperphosphatemic rats, but not affected by moderate uremia and normal serum phosphorus. Calcitriol suppressed klotho gene and protein expression in severe secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus, our study suggests that klotho may act as a positive regulator of PTH expression and secretion in secondary hyperparathyroidism.
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PMID:Increased parathyroid expression of klotho in uremic rats. 2241 41