Kale A S, Liu F, Hintz R L, Baker B K, Brewer E D, Lee P D, Durham S K, Powell D R
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Pediatr Nephrol. 1996 Aug;10(4):467-73. doi: 10.1007/s004670050141.
Serum insulin-like growth factors (IGFs), which circulate bound to specific IGF binding proteins (IGFBPs), must exit the intravascular space before acting on target tissues. Little is known about the nature of IGF/IGFBPs in extravascular fluids of patients with chronic renal failure (CRF). Peritoneal dialysate (PD) was studied since, after a short incubation, PD contains proteins which have entered an extravascular space; thus, IGF/IGFBP forms in PD are more likely than serum forms to interact with target tissues. IGF-I and IGF-II, and IGFBPs 1-4, were readily identified by specific immunoassays and/or 125iodine-IGF ligand blotting of simultaneously obtained PD and serum samples from seven CRF children; IGFBP-3 was a major IGFBP in PD as in serum. Where quantitated, IGF and IGFBP levels in PD were approximately 10% of serum concentrations. After separation of PD and serum by size-exclusion chromatography, serum had more IGFBP-3 in 150-kilodalton (kDa) than 35-kDa fractions, while PD had far less IGFBP-3 in 150-kDa than 35-kDa fractions. Immunoblot studies revealed a major 29-kDa IGFBP-3 fragment, in addition to intact 41- and 38-kDa IGFBP-3 forms, in PD and CRF serum; the 29-kDa form predominated in the 35-kDa PD fractions. These data suggest that the 29-kDa fragment is the IGFBP-3 form most likely to modulate IGF effects on target tissues of CRF individuals.
血清胰岛素样生长因子(IGFs)与特定的胰岛素样生长因子结合蛋白(IGFBPs)结合后在血液循环中运输,在作用于靶组织之前必须离开血管内空间。关于慢性肾衰竭(CRF)患者血管外液中IGF/IGFBPs的性质知之甚少。由于短时间孵育后的腹膜透析液(PD)含有进入血管外空间的蛋白质,因此对其进行了研究;因此,PD中的IGF/IGFBP形式比血清形式更有可能与靶组织相互作用。通过特异性免疫测定和/或对同时采集的7名CRF儿童的PD和血清样本进行125碘-IGF配体印迹法,很容易鉴定出IGF-I、IGF-II以及IGFBPs 1-4;与血清一样,IGFBP-3是PD中的主要IGFBP。在定量时,PD中的IGF和IGFBP水平约为血清浓度的10%。通过尺寸排阻色谱法分离PD和血清后,血清中150千道尔顿(kDa)的IGFBP-3比35-kDa组分中的更多,而PD中150-kDa的IGFBP-3比35-kDa组分中的少得多。免疫印迹研究显示,除了完整的41-kDa和38-kDa IGFBP-3形式外,PD和CRF血清中还有一个主要的29-kDa IGFBP-3片段;29-kDa形式在35-kDa的PD组分中占主导地位。这些数据表明,29-kDa片段是最有可能调节IGF对CRF个体靶组织作用的IGFBP-3形式。