Am J Physiol Renal Physiol. 2011 Oct;301(4):F745-50. doi: 10.1152/ajprenal.00037.2011. Epub 2011 Jul 6.
Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal tissue counteracts aging. Overexpression of Klotho substantially prolongs the life span. Klotho deficiency leads to excessive formation of 1,25(OH)(2)D(3), growth deficit, accelerated aging, and early death. Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. The present study explored the possibility that dehydration influences Klotho expression. Klotho transcript levels were determined by RT-PCR, and Klotho protein abundance was detected by Western blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in human embryonic kidney (HEK293) cells. Dehydration was followed by a significant decline of renal Klotho transcript levels and protein abundance, accompanied by an increase in plasma osmolarity as well as plasma ADH, aldosterone, and 1,25(OH)(2)D(3) levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 μM) significantly decreased Klotho transcription and protein expression in HEK293 cells. In conclusion, the present observations disclose a powerful effect of dehydration on Klotho expression, an effect at least partially mediated by enhanced release of ADH and aldosterone.
Klotho 是一种跨膜蛋白、蛋白酶和激素，主要在肾脏组织中表达，可抵抗衰老。Klotho 的过表达可显著延长寿命。Klotho 缺乏会导致 1,25(OH)₂D₃的过度形成、生长缺陷、加速衰老和早亡。衰老通常伴随着脱水，人们认为脱水会加速与年龄相关的疾病的发展。本研究探讨了脱水是否会影响 Klotho 表达的可能性。通过 RT-PCR 确定肾组织中 Klotho 转录本水平，并通过 Western blot 检测脱水和 36 小时脱水的小鼠以及人胚肾 (HEK293) 细胞中的 Klotho 蛋白丰度。脱水后，肾脏 Klotho 转录本水平和蛋白丰度显著下降，同时血浆渗透压以及血浆 ADH、醛固酮和 1,25(OH)₂D₃水平升高。抗利尿激素 (ADH；50 nM) 和醛固酮 (1 μM) 可显著降低 HEK293 细胞中的 Klotho 转录和蛋白表达。综上所述，本研究揭示了脱水对 Klotho 表达的强烈影响，这种影响至少部分是通过增强 ADH 和醛固酮的释放来介导的。
