Handling of low-density lipoprotein by the renal tubule: release of fragments due to incomplete degradation
| Autor: | Ashok Kumar Singh, George Dunea, Ernest Cabrera, Jose A.L. Arruda, Ravi Shankar, Alfredo A. Pegoraro, Krishnamurthy P. Gudehithlu |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Cell Membrane Permeability Kidney Cortex Nephrosis Renal function Pathology and Forensic Medicine Iodine Radioisotopes Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Humans Protamines Horseradish Peroxidase Kidney Kidney Medulla biology Glomerulonephritis General Medicine medicine.disease Protamine Rats Lipoproteins LDL Proteinuria medicine.anatomical_structure Endocrinology Kidney Tubules chemistry Receptors LDL Low-density lipoprotein LDL receptor biology.protein Chromatography Gel lipids (amino acids peptides and proteins) Electrophoresis Polyacrylamide Gel Lipoprotein |
| Zdroj: | The Journal of laboratory and clinical medicine. 139(6) |
| ISSN: | 0022-2143 |
| Popis: | Because the mechanism by which lipoproteins are processed and modified in the renal tubule in patients with nephrosis is not completely understood, we studied the handling of low-density lipoprotein (LDL) in perfused rat kidneys made permeable by protamine. Protamine pretreatment increased the clearance of 125I LDL 25-fold compared to controls, thereby simulating a proteinuric kidney. Similar studies were also conducted in kidneys of rats made proteinuric by the induction of passive Heymann nephritis. Of the perfused iodinated LDL, 5% was localized in the cortex and lesser amounts in the medulla and urine. In the cortex and medulla, iodinated LDL was present mainly in the intact form (90%); just 10% was present in the degraded form. Using horseradish peroxidase conjugated to LDL, we demonstrated specific staining in the proximal tubules, suggesting that specific LDL receptors were present in that location. Although LDL in the tissue was present mostly in the intact form, it was 95% degraded in urine, and the degradation was inhibited by chloroquine, indicating that the lysosomes were the site of LDL metabolism. Gel chromatography and electrophoresis of iodinated LDL in the urine showed the presence of fragments in the range of 5 to 15 kD. We conclude that renal degradation of LDL is incomplete and that the incompletely degraded fragments released into the urine may be toxic to the kidney by virtue of their lipid side-chains. (J Lab Clin Med 2002;139:372-8) |
| Databáze: | OpenAIRE |
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