Dërmaku-Sopjani Miribane, Sopjani Mentor, Saxena Ambrish, Shojaiefard Manzar, Bogatikov Evgenii, Alesutan Ioana, Eichenmüller Melanie, Lang Florian
Department of Physiology, University of Tübingen, Tübingen, Germany.
Cell Physiol Biochem. 2011;28(2):251-8. doi: 10.1159/000331737. Epub 2011 Aug 16.
Klotho, a transmembrane protein, protease and hormone has been shown to exert a profound effect on phosphate metabolism. Klotho overexpression lowers and Klotho deficiency increases the plasma phosphate concentration, effects in part attributed to an inhibitory effect of Klotho on the formation of 1,25-dihydroxycholecalciferol (1,25(OH) (2)D(3)), the active form of Vitamin D. Beyond that Klotho has been shown to decrease renal tubular phosphate transport more directly. The influence of Klotho on the plasma phosphate concentration contributes to the profound effect of Klotho on ageing and life span. The present study explored whether Klotho influences the major renal tubular (NaPi-IIa) and the major intestinal (NaPi-IIb) phosphate transporters. For functional analysis NaPi-IIa or NaPi-IIb were expressed in Xenopus oocytes both, without or with additional coexpression of Klotho and electrogenic phosphate transport was estimated from the phosphate-induced current (Ip). According to RT-PCR Klotho is expressed in the murine kidney and intestine. Coexpression of Klotho decreased Ip in both NaPi-IIa- and NaPi-IIb-expressing oocytes. Klotho decreased the maximal Ip without appreciably affecting the concentration required for halfmaximal Ip. Treatment of NaPi-IIa- or NaPi-IIb-expressing oocytes with Klotho protein similarly decreased Ip. In conclusion, Klotho down regulates both, renal (NaPi-IIa) and intestinal (NaPi-IIb) phosphate transporters.
klotho是一种跨膜蛋白、蛋白酶和激素，已被证明对磷酸盐代谢有深远影响。klotho过表达会降低血浆磷酸盐浓度，而klotho缺乏则会使其升高，部分影响归因于klotho对维生素D的活性形式1,25-二羟基胆钙化醇（1,25(OH)₂D₃）形成的抑制作用。除此之外，klotho已被证明能更直接地减少肾小管磷酸盐转运。klotho对血浆磷酸盐浓度的影响有助于其对衰老和寿命产生深远影响。本研究探讨了klotho是否影响主要的肾小管（NaPi-IIa）和主要的肠道（NaPi-IIb）磷酸盐转运体。为了进行功能分析，在非洲爪蟾卵母细胞中分别表达NaPi-IIa或NaPi-IIb，无论有无klotho的额外共表达，通过磷酸盐诱导电流（Ip）估算电生性磷酸盐转运。根据逆转录聚合酶链反应（RT-PCR），klotho在小鼠肾脏和肠道中表达。klotho与NaPi-IIa和NaPi-IIb共表达均降低了Ip。klotho降低了最大Ip，但对达到最大Ip一半所需的浓度没有明显影响。用klotho蛋白处理表达NaPi-IIa或NaPi-IIb的卵母细胞同样降低了Ip。总之，klotho下调了肾小管（NaPi-IIa）和肠道（NaPi-IIb）的磷酸盐转运体。
