Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2

Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2
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DOI:
10.1152/ajprenal.0139.2001
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发表时间:
2001-12-01
影响因子:
4.2
通讯作者:
Verbavatz, JM
Verbavatz, JM
中科院分区:
医学2区
文献类型:
--
作者:
Combet, S;Teillet, L;Verbavatz, JM

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在雌性WAG/Rij大鼠中研究了慢性限食预防年龄相关性多尿的机制。在衰老大鼠中观察到的肾乳头渗透压的降低不能通过食物限制来纠正。UT-A1和UT-B1尿素转运蛋白的表达显著减少,提示随意进食或限食的衰老大鼠髓内尿素含量降低。限食可部分阻止衰老大鼠内髓中水通道蛋白-2(AQP 2)的下调。AQP 2和磷酸化形式的AQP 2(p-AQP 2),其中存在的是弥漫性的细胞质内的集合管主细胞在正常喂养的衰老大鼠,优先针对在顶端区域的细胞在食物限制的衰老动物。血浆血管加压素(AVP)在10月龄和30月龄大鼠中相似,但在食物限制的30月龄大鼠中加倍。这项研究表明:1)肾脏衰老与髓质内AQP 2、UT-A1和UT-B1表达显著降低以及乳头状血管渗透压降低相关; 2)慢性食物限制通过增加血浆AVP浓度,改善AQP 2和p-AQP 2向髓质主细胞顶端膜的募集,从而预防年龄相关性多尿。
The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 (AQP2) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both AQP2 and the phosphorylated form of AQP2 (p-AQP2), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin (AVP) was similar in 10- and 30-mo-old rats fed ad libitum, but was doubled in food-restricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in AQP2, UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of AQP2 and p-AQP2 to the apical membrane in inner medulla principal cells, permitted by increased plasma AVP concentration.