α-klotho作为钙稳态的调节因子。
alpha-Klotho as a regulator of calcium homeostasis.
作者信息
Imura Akihiro, Tsuji Yoshihito, Murata Miyahiko, Maeda Ryota, Kubota Koji, Iwano Akiko, Obuse Chikashi, Togashi Kazuya, Tominaga Makoto, Kita Naoko, Tomiyama Ken-ichi, Iijima Junko, Nabeshima Yoko, Fujioka Makio, Asato Ryo, Tanaka Shinzo, Kojima Ken, Ito Juichi, Nozaki Kazuhiko, Hashimoto Nobuo, Ito Tetsufumi, Nishio Takeshi, Uchiyama Takashi, Fujimori Toshihiko, Nabeshima Yo-ichi
机构信息
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
出版信息
Science. 2007 Jun 15;316(5831):1615-8. doi: 10.1126/science.1135901.
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.
α-klotho被鉴定为一种与以寿命短为特征的早衰样表型相关的基因。在小鼠中，我们发现了α-Klotho（α-Kl）与钠钾-腺苷三磷酸酶（Na +，K + -ATPase）之间的分子关联，并为质膜上Na +，K + -ATPase丰度的增加提供了证据。低浓度的细胞外游离钙（[Ca2 +] e）以α-Kl和Na +，K + -ATPase依赖性方式快速诱导甲状旁腺激素（PTH）的分泌。由Na +，K + -ATPase活性产生的增加的Na +梯度可能与脉络丛和肾脏中的离子通道和转运蛋白协同驱动Ca2 +的跨上皮转运。我们的研究结果揭示了α-Kl在钙代谢调节中的基本作用。
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