Frey Simone K, Nagl Britta, Henze Andrea, Raila Jens, Schlosser Beate, Berg Thomas, Tepel Martin, Zidek Walter, Weickert Martin O, Pfeiffer Andreas F H, Schweigert Florian J
Institute of Nutritional Science, University of Potsdam, Potsdam-Rehbrücke, Germany.
Lipids Health Dis. 2008 Aug 27;7:29. doi: 10.1186/1476-511X-7-29.
The levels of retinol-binding protein 4 (RBP4) - the carrier protein for Vitamin A in plasma - are tightly regulated under healthy circumstances. The kidney, the main site of RBP4 catabolism, contributes to an elevation of RBP4 levels during chronic kidney disease (CKD) whereas during chronic liver disease (CLD) RBP4 levels decrease. Little is known about RBP4 isoforms including apo-RBP4, holo-RBP4 as well as RBP4 truncated at the C-terminus (RBP4-L and RBP4-LL) except that RBP4 isoforms have been reported to be increased in hemodialysis patients. Since it is not known whether CLD influence RBP4 isoforms, we investigated RBP4 levels, apo- and holo-RBP4 as well as RBP4-L and RBP4-LL in plasma of 36 patients suffering from CKD, in 55 CLD patients and in 50 control subjects. RBP4 was determined by ELISA and apo- and holo-RBP4 by native polyacrylamide gel electrophoresis (PAGE). RBP4-L and RBP4-LL were analyzed after immunoprecipitation by mass spectrometry (MALDI-TOF-MS).
RBP4 isoforms and levels were highly increased in CKD patients compared to controls (P < 0.05) whereas in CLD patients RBP4 isoforms were not different from controls. In addition, in hepatic dysfunction RBP4 levels were decreased whereas the amount of isoforms was not affected.
The occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidney function and may therefore be important in investigating kidney function and related disorders.
视黄醇结合蛋白4(RBP4)——血浆中维生素A的载体蛋白——在健康情况下受到严格调控。肾脏是RBP4分解代谢的主要部位,在慢性肾脏病(CKD)期间会导致RBP4水平升高,而在慢性肝病(CLD)期间RBP4水平会降低。除了据报道血液透析患者中RBP4异构体增加外,人们对包括脱辅基RBP4、全RBP4以及C末端截短的RBP4(RBP4-L和RBP4-LL)等RBP4异构体知之甚少。由于尚不清楚CLD是否会影响RBP4异构体,我们调查了36例CKD患者、55例CLD患者和50例对照受试者血浆中的RBP4水平、脱辅基和全RBP4以及RBP4-L和RBP4-LL。通过酶联免疫吸附测定(ELISA)测定RBP4,通过天然聚丙烯酰胺凝胶电泳(PAGE)测定脱辅基和全RBP4。通过基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)对免疫沉淀后的RBP4-L和RBP4-LL进行分析。
与对照组相比,CKD患者的RBP4异构体和水平显著升高(P < 0.05),而CLD患者的RBP4异构体与对照组无差异。此外,在肝功能障碍时,RBP4水平降低,而异构体数量不受影响。
RBP4异构体的出现不受肝功能影响,但似乎与肾功能密切相关,因此在研究肾功能及相关疾病方面可能具有重要意义。