Document Detail


Generation of fatty acids from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cardiolipin liposomes that stabilize recombinant human serum albumin.
MedLine Citation:
PMID:  23294393     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Context: At elevated temperatures, studies have shown that serum albumin undergoes irreversible changes to its secondary structure. Anionic fatty acids and/or anionic surfactants have been shown to stabilize human serum albumin (HSA) against thermal denaturation through bridging hydrophobic domains and cationic amino acids residues of the protein. Objective: As albumin can readily interact with a variety of liposomes, this study proposes that cardiolipin delivered via 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes can improve the thermal stability of recombinant HSA produced in Saccharomyces cerevisiae (ScrHSA) in a similar manner to anionic fatty acids. Materials and methods: Thermal stability and structure of ScrHSA in the absence and presence of DPPC/cardiolipin liposomes was assessed with U/V circular dichroism spectropolarimetry and protein thermal stability was confirmed with differential scanning calorimetry. Results: Although freshly prepared DPPC/cardiolipin liposomes did not improve the stability of ScrHSA, DPPC/cardiolipin liposomes incubated at room temperature for 7 d (7dRT) dramatically improved the thermal stability of the protein. Mass spectrometry analysis identified the presence of fatty acids in the 7dRT liposomes, not identified in freshly prepared liposomes, to which the improved stability was attributed. Discussion and conclusion: The generation of fatty acids is attributed to either the chemical hydrolysis or oxidative cleavage of the unsaturated acyl chains of cardiolipin. By modulating the lipid composition through the introduction of lipids with higher acyl chain unsaturation, it may be possible to generate the stabilizing fatty acids in a more rapid manner.
Authors:
Grant E Frahm; Brooke E Cameron; Jeffrey C Smith; Michael J W Johnston
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Journal of liposome research     Volume:  -     ISSN:  1532-2394     ISO Abbreviation:  J Liposome Res     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9001952     Medline TA:  J Liposome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate , Health Canada.
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