Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / cerebrospinal fluid
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Calcium / metabolism*
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Cell Membrane / enzymology
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Cell Membrane / metabolism
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Choroid Plexus / metabolism
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Cytoplasm / enzymology
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Cytoplasm / metabolism
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Endoplasmic Reticulum / metabolism
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Endosomes / metabolism
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Enzyme Inhibitors / pharmacology
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Feedback, Physiological
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Glucuronidase / genetics
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Glucuronidase / metabolism
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Glucuronidase / physiology*
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Golgi Apparatus / metabolism
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HeLa Cells
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Homeostasis*
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Humans
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Ion Transport
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Kidney / enzymology
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Kidney / metabolism
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Klotho Proteins
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Mice
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Ouabain / pharmacology
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Parathyroid Glands / enzymology
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Parathyroid Glands / metabolism
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Parathyroid Hormone / metabolism
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Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
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Sodium-Potassium-Exchanging ATPase / metabolism
Substances
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Enzyme Inhibitors
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Parathyroid Hormone
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Ouabain
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Glucuronidase
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Klotho Proteins
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Sodium-Potassium-Exchanging ATPase
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Calcium