Human apolipoprotein A-I (apoA-I) has been shown to exhibit antimicrobial activity by neutralizing lipopolysaccharides and destabilizing inner membranes of gram-negative bacteria. Previous studies showed that acrolein, a highly reactive αβ unsaturated aldehyde an environmental pollutant and an endogenously generated lipid peroxidation product, modifies ϵ-amino groups of lysine residues in apoA-I. The current study investigated the effect of acrolein exposure on the structure and antimicrobial activity of apoA-I. Acrolein modification was evident by the appearance of apoA-I oligomers due to intermolecular crosslinking, as well as reactivity with an antibody specific for acrolein. Increase of the acrolein to protein ratio resulted in heavily cross-linked apoA-I. Circular dichroism analysis showed that the α-helical content of acrolein-modified apoA-I was decreased but the protein retained α-helicity. The stability of modified proteins was increased. Phosphatidylglycerol binding was strongly affected when apoA-I was modified with acrolein. Lipopolysaccharide binding experiments showed that the binding of acrolein modified apoA-I became weaker than unmodified apoA-I. These results suggest that apoA-I modification by acrolein leads to decreased binding of apoA-I to bacterial membranes making it less potent as an antimicrobial protein.
|Advisor:||Weers, Paul M. M.|
|Commitee:||Bhandari, Deepali, Narayanaswami, Vasanthy|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 57/01M(E), Masters Abstracts International|
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