A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice = 항산화 및 항동맥경화 활성 보유 아포지단백질 변이체 V156K

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Title
A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice = 항산화 및 항동맥경화 활성 보유 아포지단백질 변이체 V156K
Author(s)
K H Cho; S H Park; Jong Min Han; Hyoung-Chin Kim; I Choi; J R Kim
Bibliographic Citation
Experimental and Molecular Medicine, vol. 39, no. 2, pp. 160-169
Publication Year
2007
Abstract
In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL- or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.
Keyword
AntioxidantsApolipoprotein A-IAtherosclerosisHDLLipoproteinsMutant proteins
ISSN
I000-0028
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/emm.2007.18
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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