Evidence for stanniocalcin binding activity in mammalian blood and glomerular filtrate
Evidence for stanniocalcin binding activity in mammalian blood and glomerular filtrate
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DOI：
10.1111/j.1523-1755.2005.67104.x
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发表时间：
2005-02-01
影响因子：
19.6
通讯作者：
Wagner, GF
中科院分区：
文献类型：
--
作者：
James, K;Seitelbach, M;Wagner, GF
背景。 50 kD 形式的激素斯钙素-1 (STC50) 广泛分布于肾脏、肺和肝脏等器官中。肾集合管细胞产生 STC50，用于局部靶向近端肾小管细胞，以增加磷酸盐重吸收。因此，当前的教条是，在大多数器官中，STC50 是一种纯粹的局部介质，不会释放到循环中。然而，肝脏肝细胞含有高水平的 STC50 及其受体，但几乎没有证据表明 STC 产生，这表明该激素实际上可能被全身递送至肝细胞。此外，之前的数据表明红细胞实际上可能与 STC 结合。在本报告中，我们试图鉴定哺乳动物血液中的 STC 结合活性。方法。在 STC 受体结合测定中分析了人、猪和狗的红细胞。还对小鼠红细胞和成年小鼠肾脏进行组织学分析，以确定 STC 配体和受体的存在。结果。在所有物种的红细胞上都鉴定出了可饱和、高亲和力的 STC 受体。更有趣的是，在肾小球滤液中也发现了 STC 结合活性，表明存在可溶、可过滤的 STC 结合蛋白。随后观察到该结合蛋白在近端直管中被重吸收。结论。这些发现表明，我们无法检测哺乳动物血清中的 STC 是因为它附着在可溶性和束缚形式的高亲和力结合蛋白上。这可能是一种将 STC 输送到远处目标的方法，也是一种从循环中去除不需要的激素的机制。
Background. The 50 kD form of the hormone stanniocalcin-1 (STC50) is widely distributed in organs such as kidney, lung, and liver. Kidney collecting duct cells produce STC50 for local targeting to proximal tubule cells to increase phosphate reabsorption. As such the current dogma is that in most organs STC50 is a purely local mediator that is not released into the circulation. However, liver hepatocytes contain high levels of both STC50 and its receptor but little evidence of STC production, suggesting that the hormone may in fact be delivered to hepatocytes systemically. Moreover, previous data suggest that red blood cells may in fact bind STC. In this report, we have sought to identify STC binding activity in mammalian blood.Methods. Human, pig, and dog red blood cells were analyzed in STC receptor binding assays. Mouse red blood cells and adult mouse kidney were also analyzed histologically for the presence of STC ligand and receptor.Results. Saturable, high affinity STC receptors were identified on red blood cells from all species. More intriguingly, STC binding activity was also identified in glomerular filtrate, indicative of a soluble, filterable STC binding protein. This binding protein was subsequently observed being reabsorbed in proximal straight tubules.Conclusion. These findings suggest that our inability to detect STC in mammalian serum is due to its being attached to soluble and tethered forms of a high-affinity binding protein. This could be a means of delivering STC to distant targets as well as a mechanism for removing unwanted hormone from the circulation.