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)

Although the pathogenesis of the diabetes mellitus syndrome remains poorly understood, both insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus predispose the individual to a similar spectrum of complications, including hypertension, macrovascular and microvascular disease, cataracts cardiomyopathy, neuropathy, and premature aging, suggesting that these complications develop along a pathway common to both diabetic conditions. Yet not all diabetic persons are affected by all of these complications or to the same degree. What causes this marked variability in the clinical manifestations of the diabetes syndrome remains an enigma. Accumulating data from animal models of diabetes and from studying patients with diabetes reveal that intracellular calcium levels are increased in most tissues. The activities of the membrane, adenosine triphosphatase (ATPase) associated cation pumps, which determine intracellular calcium level (i.e., calcium-ATPase and [sodium + potassium]-ATPase), are also altered. The nature of the alteration is often tissue specific and may depend on the level of blood glucose or insulin, or both. In this review we discuss the potential contribution of these changes in intracellular calcium regulation, whether acquired or genetically determined, to the pathogenesis of the diabetes syndrome, to the abnormalities in insulin secretion and action (mainly in non-insulin-dependent diabetes), and to the complications of both diabetes syndromes. Altered intracellular calcium metabolism may represent a common, underlying abnormality linking the metabolic, cardiovascular, ocular, and neural manifestations of the diabetic disease process.
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PMID:Diabetes mellitus: a disease of abnormal cellular calcium metabolism? 762 30

alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan. In mice, we found the molecular association of alpha-Klotho (alpha-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an alpha-Kl- and Na+,K+-ATPase-dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of alpha-Kl in the regulation of calcium metabolism.
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PMID:alpha-Klotho as a regulator of calcium homeostasis. 1756 64

Cockayne syndrome (CS) is a rare human disorder characterized by pathologies of premature aging, neurological abnormalities, sensorineural hearing loss and cachectic dwarfism. With recent data identifying CS proteins as physical components of mitochondria, we sought to identify protein partners and roles for Cockayne syndrome group B (CSB) protein in this organelle. CSB was found to physically interact with and modulate the DNA-binding activity of the major mitochondrial nucleoid, DNA replication and transcription protein TFAM. Components of the mitochondrial transcription apparatus (mitochondrial RNA polymerase, transcription factor 2B and TFAM) all functionally interacted with CSB and stimulated its double-stranded DNA-dependent adenosine triphosphatase activity. Moreover, we found that patient-derived CSB-deficient cells exhibited a defect in efficient mitochondrial transcript production and that CSB specifically promoted elongation by the mitochondrial RNA polymerase in vitro. These observations provide strong evidence for the importance of CSB in maintaining mitochondrial function and argue that the pathologies associated with CS are in part, a direct result of the roles that CSB plays in mitochondria.
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PMID:Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation. 2274 67