ApoA-I mutants V156K and R173C promote anti-inflammatory function and antioxidant activities = 아포A-I 변이체 V156K와 R173C의 항염증기능과 항산화작용 조절

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Title
ApoA-I mutants V156K and R173C promote anti-inflammatory function and antioxidant activities = 아포A-I 변이체 V156K와 R173C의 항염증기능과 항산화작용 조절
Author(s)
K H Cho; S H Park; Jong Min Han; Hyoung-Chin Kim; Y K Choi; I Choi
Bibliographic Citation
European Journal of Clinical Investigation, vol. 36, no. 12, pp. 875-882
Publication Year
2006
Abstract
Background: Two mutants of apolipoprotein (apo) A-I, V156K and A158E, showed markedly different structural and functional properties in lipid-free and lipid-bound states in the authors' earlier report. The physiological activities of these mutants were compared with the wild-type (WT) and R173C mutant using in vitro and in vivo experiments. Materials and methods: A reconstituted high-density lipoprotein (rHDL) with palmitoyloleoyl phosphatidylcholine (POPC), combined with each of the apoA-I variants, was injected into the tail-veins of hypercholesterolaemic mice (C57BL6/J), which had been fed a high cholesterol and high fat (HCHF; 0.5% cholesterol, 15% lard, 0.1% sodium cholate) diet for 23 weeks, once at 0 h and then every 24 h, at a dosage of 30 mg apoA-I kg -1 of body-weight. Results: The V156K-rHDL and R173C-rHDL exhibited significantly stronger anti-oxidant activity against copper-mediated low-density lipoprotein (LDL) oxidation than did A158E in an apolipoprotein state. The mice injected with WT-rHDL or A158E-rHDL showed abrupt increases in total cholesterol concentrations (47% and 38%, respectively) as compared with the levels before injection, whereas the mice injected with V156K-rHDL and R173C-rHDL did not. Injection with V156K-rHDL improved serum lipids and anti-oxidative activities compared with the injection of WT-rHDL. Injection of WT-rHDL or A158E-rHDL increased serum interleukin-6 (IL-6) to 90-110 pg mL -1, whereas the injection of V156K-rHDL or R173C-rHDL increased serum IL-6 to 17-25 pg mL-1 only. Conclusion: The V156K-rHDL and R173C-rHDL displayed potent beneficial effects, including anti-oxidant and anti-inflammatory activity from both in vitro and in vivo evaluations, whereas the WT-rHDL and A158E-rHDL did not.
Keyword
Apolipoprotein A-IHDL-therapyPoint mutantReconstituted HDL
ISSN
0014-2972
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1365-2362.2006.01737.x
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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