ISSN:
1573-904X
Keywords:
lipid transfer protein I
;
cyclosporine
;
lipoproteins
;
triglycerides
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. The purpose of this study was to determine if lipid transfer protein (LTP I) facilitated triglyceride (TG) transfer activity regulates the plasma lipoprotein distribution of cyclosporine (CSA). Methods. To assess the influence of drug concentration and incubation time on the plasma lipoprotein distribution of CSA, 3H-CSA (50 to 1000 ng/ml) was incubated in human plasma for 5 to 120 minutes at 37°C. To determine if LTP I facilitated TG transfer activity regulates the plasma lipoprotein distribution of CSA, 3H-Triolein (TG)- or 3H-CSA-enriched high-density lipoproteins (HDL) or low-density lipoproteins (LDL) were incubated in T150 buffer (50 mM Tris-HCl, 150 mM NaCl, 0.02% Sodium Azide, 0.01% Disodium EDTA), pH 7.4 which contained a 3H-Triolein (TG) or 3H-CSA-free lipoprotein counterpart ± exogenous LTP I (1.0 μg protein/ml) or in delipidated human plasma which contained 1.0 μg protein/ml of endogenous LTP I for 90 minutes at 37°C. These experiments were repeated in the presence of a monoclonal antibody TP1 (15 μg protein/ml) directed against LTP I. Results. No differences in CSA lipoprotein distribution were observed following incubation of the drug at varying concentrations and incubation times in human plasma. The percent transfer of TG from HDL to LDL and LDL to HDL was greater in T150 buffer than in human plasma. However, the percent transfer of CSA from only LDL to HDL was greater in T150 buffer than in human plasma. Furthermore, undetectable 3H-CSA transfer from HDL to LDL in T150 buffer containing purified LTP I was observed. In addition, when the percent transfer of TG and CSA were determined in the presence of TP1, the percent transfer of TG and CSA from only LDL to HDL were significantly decreased in T150 buffer and human plasma compared to controls. Conclusions. These findings suggest that the transfer of CSA between different lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018991917799
Permalink