Cyclosporine binds to the neutral lipid and potentially other binding sites of lipid transfer protein I
The objective of this study was to determine if cyclosporine (CSA) binds directly to the neutral lipid-binding site of lipid transfer protein I (LTP I). This was accomplished by determining LTP I concentrations and cholesteryl esters (CE) and CSA radioactivity of eluted fast protein liquid chromatog...
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Published in | Pharmaceutical research Vol. 20; no. 7; pp. 1009 - 1014 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Springer
01.07.2003
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | The objective of this study was to determine if cyclosporine (CSA) binds directly to the neutral lipid-binding site of lipid transfer protein I (LTP I).
This was accomplished by determining LTP I concentrations and cholesteryl esters (CE) and CSA radioactivity of eluted fast protein liquid chromatography (FPLC) fractions following an injection of different treatment groups (i.e., LTP I alone, 3H-CE liposomes alone, 3H-CSA liposomes alone, 3H-CE liposomes + LTP I, and 3H-CSA liposomes + LTP I) onto an FPLC column. Our hypothesis is that CSA will bind to the neutral lipid-binding site of LTP I because of its high solubility/interaction with cholesterol and triglycerides.
Coincubation of LTP I with 3H-CE liposomes resulted in a significant decrease in the LTP I peak reported at fraction 10 and the appearance of a broad LTP I peak at fractions 30-34 compared to control. Coincubation of LTP I with 3H-CSA liposomes resulted in a significant decrease in the LTP I peak reported at fraction 10 and fraction 30 compared to control. In addition, 30% of the original radioactivity associated with 3H-CSA liposomes was found coeluted with the unbound LTP I peak at fraction 10. Taken together, these findings suggest that CSA does bind to the neutral lipid-binding site of LTP I but may also bind to other regions along the LTP I molecule.
We have determined that LTP I mediated transfer of CSA between lipoproteins may be a result of the direct binding of CSA to LTP I at both its neutral binding site and potentially other binding sites along the molecule. These findings provide further evidence that the distribution/redistribution of drugs among plasma lipoproteins facilitated by LTP I may serve as a possible mechanism for determining the ultimate fate of drug compounds. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0724-8741 1573-904X |
DOI: | 10.1023/A:1024454105124 |