Effects of apolipoprotein E deficiency on sphingosine-1-phosphate distribution in plasma and lipoproteins of mice
10.3760/cma.j.issn.0253-3758.2017.05.011
- VernacularTitle: 载脂蛋白E基因敲除对小鼠脂蛋白上鞘氨醇-1-磷酸分布的影响
- Author:
Xinquan YANG
1
;
Yang YU
;
Shoudong GUO
;
Yingjie CUI
;
Guoliang HU
;
Lei FENG
;
Daxin WANG
;
Shucun QIN
Author Information
1. Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha 410011, China
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Apolipoprotein E;
Mice, knockout;
Lipoproteins
- From:
Chinese Journal of Cardiology
2017;45(5):419-426
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of apolipoprotein E deficiency (Apo E-/-) on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice.
Methods:Five male or female Apo E-/- or wild type (WT) mice were fed with chow diet and sacrificed at 32-week-age and plasma was collected. The constituents of lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein concentration of constituents was detected by BCA protein quantitative kit, and the S1P concentration in plasma and various lipoprotein constituents was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was used to determine the plasma, liver, and kidney protein expression of apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P concentration in plasma and various constituents of lipoprotein in the Apo E-/- mice was compared to respective WT mice.
Results:(1)Plasma S1P content was significantly higher in the Apo E-/- groups than that of WT groups (male: (535.7±78.5)nmol/L vs. (263.3±22.0)nmol/L; female: (601.1±64.0)nmol/L vs. (279.0±33.9)nmol/L; all P<0.01). (2) Compared with WT mice, S1P content in non-HDL(LDL+ VLDL) was significantly higher in Apo E-/- mice (male: (504.9±52.8)nmol/L vs. (28.7±9.0)nmol/L; female: (427.7±27.4) vs. (27.8±4.7)nmol/L; after standardization of protein concentration, male: (385.0±41.2)pmol/mg protein vs. (71.4±6.6)pmol/mg protein; female: (330.2±22.0)pmol/mg protein vs. (67.2±12.1)pmol/mg protein; all P<0.01). (3) The expression of Apo M in plasma, liver and kidney was significantly higher in Apo E-/- groups than that of WT groups(all P<0.05).
Conclusion:The deficiency of Apo E could lead to upregulated S1P expression in the non-HDL, the underlying mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.
