title: Cyclosporine binds to the neutral lipid and potentially other binding sites of lipid transfer protein I.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Mona
authors.initials: M
authors.lastname: Kwong
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000704:Analysis of Variance; D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D016572:Cyclosporine / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D006801:Humans
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; C422456:Ltp1 protein, barley; D016572:Cyclosporine