The apoA-I mimetic peptide 4F protects apolipoprotein A-I from oxidative damage. (March 2019)

• Record Type: Journal Article
• Authors: White, C. Roger; Datta, Geeta; Wilson, Landon; Palgunachari, Mayakonda N.; Anantharamaiah, G.M.
• Is Part Of: Chemistry and physics of lipids. Volume 219(2019)
• Page Start: 28
• Page End: 35
• Publication Date: 2019-03
• Subjects: ApoA-I -- ApoA-I mimetic peptide -- Hypochlorous acid -- Oxidation -- Cholesterol efflux; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2019.01.009
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: New nanoparticles using human apoA-I and well-characterized apoA-I mimetic peptide 4F with POPC in the absence of chemical detergents. Presence of 4F in nanoparticles potentially enhances biological activities of human apoAI:lipid nanoparticles. New nanoparticles are stable to oxidative process. ApoA-I-4F:POPC nanoparticles potentially ameliorate lipid-mediated disorders more effectively than apoA-I:POPC nanodiscs. Abstract: High density lipoprotein (HDL) is prone to modification by the oxidizing and chlorinating agent hypochlorite anion (OCl − ). Oxidation of apolipoprotein (apo) A-I, the major protein in HDL, reduces ABCA-1 mediated cholesterol efflux and other protective responses to HDL. The apoA-I mimetic peptide 4F has been shown to undergo oxidation; however, the ability of the peptide to mediate cholesterol efflux remains intact. Here, we show that 4F protects apoA-I from hypochlorite-mediated oxidation. Mass spectral analysis of apoA-I shows that tyrosine residues that are prone to hypochlorite-mediated chlorination are protected in the presence of 4F. Furthermore, 4F enhances the cholesterol efflux ability of apoA-I to a greater extent than either 4F or apoA-I alone, even after hypochlorite oxidation. These observations suggest that apoA-I in lipid complexes may be protected by the presence of 4F, resulting in the preservation of its anti-inflammatory and anti-atherogenic properties. These studies also form the basis for the future studies of nanoparticles possessing both apoA-I and 4F.