Odera Keiko, Goto Sataro, Takahashi Ryoya
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Biogerontology. 2007 Oct;8(5):505-15. doi: 10.1007/s10522-007-9093-7. Epub 2007 Apr 24.
Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.
巨蛋白和立方蛋白是负责重吸收肾近端小管中肾小球滤过蛋白（尤其是白蛋白）的主要内吞受体。为了更好地理解大鼠蛋白尿随年龄增长的发生机制，我们研究了肾脏中这两种受体的数量和细胞定位随年龄的变化。对肾脏提取物的免疫印迹分析表明，巨蛋白的量随年龄显著减少。虽然完整立方蛋白的量没有与年龄相关的变化，但立方蛋白片段的量随年龄增加。免疫组织化学研究显示，巨蛋白和立方蛋白在幼年大鼠近端小管细胞的刷状缘膜中主要定位，但在老年大鼠中这些受体倾向于扩散到细胞质中。有趣的是，除了近端小管细胞外，肾小球细胞中也存在少量但显著量的巨蛋白和立方蛋白。随着年龄增长，肾小球中受体的数量逐渐增加。这种与年龄相关的增加可能是为了弥补近端小管对白蛋白摄取的与年龄相关的缺陷。因此，虽然尚不清楚肾小球中的巨蛋白和立方蛋白是否有助于原尿中白蛋白的摄取，但尿中白蛋白量与年龄相关的增加可能至少部分归因于近端小管中这两种受体的数量和质量改变。
