| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print April 4, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00752.2001
Submitted on December 20, 2001
Accepted on April 2, 2002
1 Divisions of Gastroenterology and Hepatology, Department of Medicine, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA
2 Division of Nephrology, Department of Medicine, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA
3 Department of Radiation Oncology, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA
4 Department of Biochemistry, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA
5 Divisions of Gastroenterology and Hepatology, Department of Medicine, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA; Division of Nephrology, Department of Medicine, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA; Department of Biochemistry, Medical College Of Wisconsin and Veterans Administration Medical Center, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: SEETHARA{at}MCW.EDU.
The role of renal apical brush border membrane (BBM) endocytic receptors, cubilin, and megalin in the onset of albuminuria in rats exposed to a single-dose of total body irradiation (TBI) has been investigated. Albuminuria was evident as immunoblot (IB) analysis of the urine samples from TBI rats revealed excretion of large amounts of albumin. IB analysis of the BBM proteins did not reveal any significant changes in cubilin or megalin levels but I125-albumin binding to BBM from TBI rats declined by 80% with a 5-fold decrease (from 0.5 µM to 2.5 µM) in the affinity for albumin. IB analysis of cubilin from the BBM demonstrated a 75% loss when purified using albumin, but not IF-Cbl ligand affinity chromatography. Immunoprecipitation (IP) of Triton X-100 extract of the BBM with antiserum to cubilin followed by IB of the immune complex with an antiserum to megalin revealed a 75% loss of association between megalin and cubilin. IP studies with antiserum to cubilin or megalin and IB with antiserum to the cation-independent mannose 6-phosphate/insulin-like growth factor II-receptor (CIMPR) revealed that CIMPR interacted with both cubilin and megalin. In addition, TBI did not disrupt the association of CIMPR with either cubilin or megalin in BMM. These results suggest that albuminuria noted in TBI rats is due to selective loss of albumin and megalin, but not CIMPR or IF-Cbl, binding by cubilin. Furthermore, these results also suggest that albumin and IF-Cbl binding to cubilin occur at distinct sites and that in the rat renal BBM, CIMPR interacts with both cubilin and megalin.
This article has been cited by other articles:
|
|
 |
|
  Y. Antov, A. Barbul, H. Mantsur, and R. Korenstein Electroendocytosis: Exposure of Cells to Pulsed Low Electric Fields Enhances Adsorption and Uptake of Macromolecules Biophys. J., March 1, 2005; 88(3): 2206 - 2223. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
