Importance of a Novel Oxidative Mechanism for Elimination of Intracellular Cholesterol in Humans

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 16 Số 2 - Trang 208-212 - 1996
Erik Lund1, Olof Andersson2, Jie Zhang3, Amir Babiker4, Gunvor Ahlborg5, Ulf Diczfalusy6, Kurt Einarsson7, Jan Sjövall8, Ingemar Björkhem8
1Erik Lund From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
2Olof Andersson From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
3Jie Zhang From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
4Amir Babiker From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
5Gunvor Ahlborg From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
6Ulf Diczfalusy From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
7Kurt Einarsson From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
8From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.

Tóm tắt

Abstract We have recently demonstrated that cultured human alveolar macrophages efficiently convert cholesterol into excretable 27-oxygenated products. We show here that increasing the intracellular concentration of cholesterol by a factor of 10 leads to about a twofold increase in the excretion of 27-oxygenated products from cultured macrophages. Inhibition of the sterol 27-hydroxylase caused a significant intracellular accumulation of cholesterol. A direct comparison was made between flux of cholesterol and 27-oxygenated products from macrophages preloaded with [4- 14 C]cholesterol. Under the specific conditions employed with fetal calf serum in the culture medium, the flux of 27-oxygenated products was about 10% of that of cholesterol. Since the sterol 27-hydroxylase, which converts cholesterol to 27-oxygenated products, is present in many cell types, we suggest that 27-oxygenation is a general mechanism for removal of intracellular cholesterol. To evaluate this hypothesis, we measured the net uptake by the human liver of circulating 27-oxygenated products, which was found to be about 20 mg/24 h. This uptake corresponds to ≈4% of the bile acid production, assuming quantitative conversion into bile acids. It is concluded that the 27-hydroxylase pathway is of significance for elimination of extrahepatic cholesterol.

Từ khóa


Tài liệu tham khảo

10.1038/343425a0

1978, Surgery, 84, 1

10.1073/pnas.91.18.8592

1982, J Lipid Res, 23, 627, 10.1016/S0022-2275(20)38127-X

1988, J Lipid Res, 29, 629, 10.1016/S0022-2275(20)38509-6

1992, J Lipid Res, 33, 455, 10.1016/S0022-2275(20)41612-8

10.1172/JCI112633

1989, Biochem Int, 18, 615

10.1016/S0021-9258(18)83172-6

Zhang J Larsson O Sjövall J. 7α-Hydroxylation of 27-hydroxycholesterol and 25-hydroxycholesterol in human fibroblast cultures. 13th International Bile Acid Meeting Falk Symposium No. 80 . San Diego Calif; 1994:86.

10.1016/0041-008X(86)90231-0

1992, J Biol Chem, 267, 25092, 10.1016/S0021-9258(19)74010-1

10.1093/clinchem/28.1.5

10.1006/abio.1995.1110

10.1002/hep.1840170308

10.1073/pnas.73.9.3178

10.1042/bj2930203

1994, J Lipid Res, 35, 1026, 10.1016/S0022-2275(20)40099-9

10.1152/jappl.1994.76.3.1037

Björkhem I. Mechanism of bile acid biosynthesis in mammalian liver. In: Danielsson H Sjövall J eds. Comprehensive Biochemistry . Amsterdam Netherlands: Elsevier Publishing Co; 1985:231-278.

1982, J Lipid Res, 23, 1020, 10.1016/S0022-2275(20)38074-3

Axelson M Mörk B Sjövall J. Differential distribution of unconjugated C 27 -bile acids in bile and blood. In: Paumgartner G Stiehl A Gerok W eds. Trends in Bile Acid Research . London UK: Kluwer Academic Publishers; 1988:79-88.

Björkhem I Muri-Boberg K. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Scriver CR Beaudet AL Sly WS Valee D eds. The Metabolic Basis of Inherited Diseases . New York NY: McGraw-Hill; 1994:2073-2100.

10.1016/0021-9150(73)90131-7

Thông tin
Thông tin xuất bản

Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 16 Số 2

208-212

Thông tin tác giả