Premium
ApoA‐I mutants V156K and R173C promote anti‐inflammatory function and antioxidant activities
Author(s) -
Cho K. H.,
Park S. H.,
Han J. M.,
Kim H. C.,
Choi Y. K.,
Choi I.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01737.x
Subject(s) - chemistry , popc , apolipoprotein b , cholesterol , in vivo , phosphatidylcholine , antioxidant , medicine , endocrinology , lipoprotein , high density lipoprotein , biochemistry , phospholipid , biology , microbiology and biotechnology , membrane
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.