Ruge Toralph, Neuger Lucyna, Sukonina Valentina, Wu Gengshu, Barath Stefan, Gupta Jitendra, Frankel Barbara, Christophersen Bjørn, Nordstoga Knut, Olivecrona Thomas, Olivecrona Gunilla
Department of Medical Biosciences, Physiological Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Am J Physiol Renal Physiol. 2004 Dec;287(6):F1131-9. doi: 10.1152/ajprenal.00089.2004. Epub 2004 Aug 3.
Much evidence points to a relationship among kidney disease, lipoprotein metabolism, and the enzyme lipoprotein lipase (LPL), but there is little information on LPL in the kidney. The range of LPL activity in the kidney in five species differed by >500-fold. The highest activity was in mink, followed by mice, Chinese hamsters, and rats, whereas the activity was low in guinea pigs. In contrast, the ranges for LPL activities in heart and adipose tissue were less than six- and fourfold, respectively. The activity in the kidney (in mice) decreased by >50% on food deprivation for 6 h without corresponding changes in mRNA or mass. This decrease in LPL activity did not occur when transcription was blocked with actinomycin D. Immunostaining for kidney LPL in mice and mink indicated that the enzyme is produced in tubular epithelial cells. To explore the previously suggested possibility that the negatively charged glomerular filter picks up LPL from the blood, bovine LPL was injected into rats and mice. This resulted in decoration of the glomerular capillary network with LPL. This study shows that in some species LPL is produced in the kidney and is subject to nutritional regulation by a posttranscriptional mechanism. In addition, LPL can be picked up from blood in the glomerulus.
大量证据表明肾脏疾病、脂蛋白代谢和脂蛋白脂肪酶(LPL)之间存在关联,但关于肾脏中LPL的信息却很少。五个物种肾脏中LPL活性范围相差超过500倍。活性最高的是水貂,其次是小鼠、中国仓鼠和大鼠,而豚鼠的活性较低。相比之下,心脏和脂肪组织中LPL活性范围分别小于6倍和4倍。(小鼠)肾脏中的活性在禁食6小时后降低了50%以上,而mRNA或蛋白量没有相应变化。当用放线菌素D阻断转录时,LPL活性并未降低。对小鼠和水貂肾脏LPL进行免疫染色表明,该酶是由肾小管上皮细胞产生的。为了探究之前提出的带负电荷的肾小球滤过膜从血液中摄取LPL的可能性,将牛LPL注射到大鼠和小鼠体内。这导致肾小球毛细血管网络被LPL覆盖。本研究表明,在某些物种中,LPL在肾脏中产生,并受转录后机制的营养调节。此外,LPL可在肾小球中从血液中摄取。